RnDSy-lu-2945 Immuno-Oncology Immuno-Oncology: Identifying Next Generation Targets for Cancer Immunotherapy T cell activation requires two signals: 1) recognition of the antigenic molecules, including members of the butyrophilin, CD2/SLAM, TIM, peptide/major histocompatibility complex (MHC) by the T cell receptor CD226, and TNF receptor families, along with additional members of (TCR) and 2) antigen-independent co-stimulation induced by the B7/CD28 families such as B7-H2/ICOS Ligand, B7-H3, B7-H4, interactions between co-signaling molecules expressed on antigen- and VISTA/B7-H5. Others, such as CD47/SIRP-a, Indoleamine-2,3- presenting cells (APCs) and their T cell-expressed receptors. In dioxygenase (IDO), LAG-3, leukocyte immunoglobulin-like receptors addition, T cell activation can be negatively regulated by co-inhibitory (LILR), CD94/NKG2A, and killer immunoglobulin receptors (KIR) are molecules present on APCs, which is crucial for maintaining self- molecules commonly expressed by macrophages, dendritic cells, T tolerance and regulating the duration and magnitude of immune cells, and/or natural killer (NK) cells that have also been found to be responses. Tumors frequently exploit these negative regulatory utilized by tumor cells to negatively regulate anti-tumor immune pathways, known as immune checkpoints, to evade the host’s responses. immune system. As a result, researchers have focused on targeting these pathways for cancer immunotherapy using either agonists of Target Celll co-stimulatory receptors or antagonists of inhibitory receptors to magnify the antigen-specific T cell response. Some of these studies have shown remarkable promise, but have also shed light on some MHC significant obstacles that need to be addressed. For example, monoclonal antibodies directed against the T cell co-inhibitory receptors, CTLA-4 and PD-1 have been shown to have potent anti-tumor effects, but blocking CTLA-4 or PD-1/PD-L1 has proven to ignal 2 be effective in only a minority of patients. Furthermore, researchers ignal 1 have found that patients that do respond, can become resistant or relapse after an initial positive response due to an upregulation of other immune checkpoint pathways. As a result, additional immune TCR-CD Complex checkpoint regulators that may serve as immunotherapeutic targets, either alone or in combination, are being sought. Many of these emerging targets also function as T cell co-inhibitory or co-stimulatory T Cell
Members of the B7/CD28 Families of T Cell Co-Signaling Molecules have been Successfully Targeted for Cancer Immunotherapy
Co-stimulatory Co-inhibitory Ig uperfamily
Target Cell T Cell Target Cell T Cell
B7-1/CD80 B7-H1/PD-L1 B7-1/CD80 CD28 B7-2/CD86 CTLA-4 B7-2/CD86 B7-H1/PD-L1 B7-H2/ICO L B7-1/CD80 PD-L2/B7-DC ICO PD-1 B7-H1/PD-L1 B7/CD28 Families 2Ig B7-H (Mouse) 4Ig B7-H (Human) 2Ig B7-H (Mouse) Unknown Unknown Receptors B7-H4 Receptors 4Ig B7-H (Human) B7-H /VI TA V IG8 V IG B7-H /VI TA B7-H7 (Human) CD28H B7-H7 Unknown Receptor BTLA HVEM CD160
B7 and CD28 Family Interactions Regulate T Cell Activation. Interactions between B7 family proteins and T cell-expressed immune receptors belonging to the CD28 family (CD28, CTLA-4, PD-1, ICOS, and BTLA) can transduce both T cell co-stimulatory and co-inhibitory signals, as well as have bidirectional effects (indicated by the two-headed arrows). Tumor cells frequently overexpress B7 family proteins that negatively regulate T cell activation, allowing them to inhibit anti-tumor immune responses. As blocking antibodies against CTLA-4, PD-1, and PD-L1 have been shown to improve the immune response in multiple different cancer models, additional molecules belonging to the B7 and CD28 families are being investigated as targets for cancer immunotherapy. Others Molecules Involved in Regulating T Cell Activation May Serve as Next Generation Immuno-Oncology Targets
Co-stimulatory Co-inhibitory Ig uperfamily
Target Cell T Cell Target Cell T Cell
BTN1A1 Unknown BTN2A2 Receptors
BTNL8 Unknown Unknown Ligand BTN A1 (Human) Receptor Butyrophilins BTN A1 Unknown BTNL1 (Mouse) Receptors
BTNL2
CD48/ LAM 2 (Mouse and Rat) CD2 CD 8/L A- 2B4/CD244/ LAM 4 (Human) SLAM Family CD48/ LAM 2 LAM/CD1 0 LAM/CD1 0
TIM-4 Unknown Receptor TIM-4 TIM-1 TIM Family Galectin-9 TIM-
Nectin-2/CD112 Nectin-2/CD112 Nectin and DNAM-1/CD226 Nectin-like CD1 /PVR TIGIT Binding Receptors CD1 /PVR Nectin- /CD11
TN uperfamily Target Cell T Cell
CD40 CD40 L
HVEM LIGHT Domain Key Type L Ig V-like Domain LIGHT HVEM Ig C-like Domain TL1A DR Ig I-like Domain Carbohydrate Recognition Domain C-type Lectin Domain
4-1BB L 4-1BB Mucin-like Domain B 0.2 Domain CD27 L/CD70 CD27 Immunoreceptor tyrosine-based switch motif (IT M) Immunoreceptor tyrosine-based inhibitory motif (ITIM) CD 0 L CD 0 Type V Immunoreceptor tyrosine-based activation motif (ITAM) GPI linkage GITR L GITR xxM Motif OX40 L OX40
Several Members of the Butyrophilin, CD2/SLAM, TIM, CD226, and TNF Receptor Families Regulate T Cell Co-Signaling and are being Investigated as Next Generation Targets for Cancer Immunotherapy. In addition to members of the B7/CD28 families, molecules belonging to several other families including members of the butyrophilin, CD2/SLAM, TIM, CD226, and TNF receptor families, have also been shown to regulate T cell activation. As a result, these molecules are being investigated as potential next generation immuno- oncology targets.
Learn more | rndsystems.com/pathways_tcellcosignaling Additional Emerging Immuno-Oncology Targets
Immune Cell Stimulatory Targets Immune Cell Inhibitory Targets
Target Cell NK Cell Target Cell NK Cell
HLA-C2 (2DL1) KIR2DL1 HLA-G KIR2DL4 KIR2DL2 cRγ KIR2DL HLA-C1 (2DL2/L ) KIR2D 1 HLA-C (2D 1) KIR2D 2 Unknown KIR2DL A KIR2D KIR2DL B Unknown KIR2D 4 (2D 2-2D ) DAP12 KIR2D KIR Family HLA-B 4 ( DL1) KIR DL1 KIR DL2 KIR D 1 Unknown HLA-A ( DL2) DAP12
Unknown KIR DL
KIR2DL4 HLA-G cRγ
Target Cell NK Cells Target Cell NK or T Cells
CD94-NKG2C/E CD94-NKG2 Family CD94-NKG2A HLA-E DAP12 HLA-E
Target Cell Immune Cells Target Cell Immune Cells
HLA-B27 LILRA1 HLA-C MHC Class I LILRB1 cRγ ANGPTL 100A8 Microbially-cleaved 100A9 Immunoglobulins LILRA2 cRγ MHC Class I LILRB2 ANGPTL ANGPTL HLA-C LILRA LILR Family ANGPT/ANGPTL Unknown LILRB LILRA4 γ Unknown B T-2 cR LILRB4 ANGPTL ANGPTL LILRA Unknown cRγ MHC Class I LILRB LILRA6 Unknown ANGPTL cRγ
Target Cell NK Cells, B Cells, T Cells, Dendritic Cells
Collagen LAIR-1 • Inhibition of NK cell-mediated cytotoxicity • Inhibition of BCR-, TCR-mediated activation Multiple Additional Molecules that Regulate the Activities of a Variety of Other Immune Cell Types are also being Investigated as Emerging Cancer Immunotherapy Targets. In Tregs and CD8+ T Cells addition to the molecules that regulate T cell activation, multiple molecules involved in MHC Class II regulating the activities of a variety of other immune cell types are also being investigated Galectin- LAG- as potential immuno-oncology targets. These include members of the killer • Enhanced Treg suppressive activity immunoglobulin-like receptor (KIR) family and the leukocyte immunoglobulin-like receptor L- electin • Reduced proliferation of CD8+ T cells A/B (LILRA/B) family, CD94-NKG2 heterodimeric receptors, CD47/SIRP-a, Indoleamine- 2,3-dioxygenase (IDO), and LAG-3. The KIR family and CD94-NKG2 heterodimeric receptors are both primarily expressed by natural killer (NK) cells, while both the immune Macrophages and Dendritic Cells stimulatory and inhibitory LILRA/B receptors are expressed by a much wider range of α hematopoietic cell types, including monocytes, macrophages, dendritic cells, T cells, IRP- NK cells, B cells, and granulocytes. SIRP-a and IDO are primarily expressed by • uppression of phagocytosis macrophages and dendritic cells. LAG-3 is expressed on regulatory T cells (Tregs), along • ormation of Tregs with CD8+ T cells. LAIR-1 is expressed by NK cells, B cells, T cells, and dendritic cells. The effects of each of these molecules on the different immune cell types is indicated in the Tryptophan • Impairment of T cell proliferation figure. The domain key for the structures is located on the previous page. IDO Kynurenine • Induction of Th1 cell apotosis • Treg Differentiation Products for Studying Immuno-Oncology Targets Recombinant Proteins R&D Systems offers an unparalleled selection of recombinant proteins that can be used to characterize the effects of immuno-oncology targets. Our stringent production and purification standards ensure that R&D Systems® proteins will provide researchers with industry-leading bioactivity, low endotoxin levels, and lot-to-lot consistency. In addition to our standard recombinant proteins, we also offer Animal-Free™ and Animal Component-Free Process recombinant proteins, GMP-grade recombinant proteins, and custom protein development services.
B7/CD28 Families B7/CD28 Families Molecule Species Source Tag Catalog # Molecule Species Source Tag Catalog # Human NS0 Fc, His 140-B1 B7-H7/HHLA2 Human HEK293 Fc 8084-B7 Human HEK293 His 9050-B1 Human NS0 Fc 8385-BT Mouse NS0 Fc, His 740-B1 BTLA Human HEK293 His 9235-BT B7-1/CD80 Mouse NS0 His 9014-B1 Mouse NS0 Fc 3007-BT Rat NS0 Fc 1214-B7 BTLA (aa 31–153) Human HEK293 Fc 9509-BT Cynomolgus Human/ HEK293 His 9244-B1 monkey Cynomolgus NS0 Fc 342-CD monkey/Rhesus Human NS0 Fc, His 141-B2 CD28 macaque Human CHO Fc 7625-B2 Mouse NS0 Fc, His 483-CD B7-2/CD86 Human HEK293 His 9090-B2 Human HEK293 Fc 8316-TR Mouse Sf21 (baculovirus) Fc 741-B2 CD28H/TMIGD2 Human HEK293 His 9236-TR Rat NS0 Fc 1340-B2 Human Sf21 (baculovirus) Fc, His 325-CT Human NS0 Fc 156-B7 Human CHO Fc 7268-CT Human HEK293 His 9049-B7 CTLA-4 Mouse NS0 Fc, His 434-CT Mouse NS0 Fc 1019-B7 B7-H1/PD-L1 Cynomolgus HEK293 Fc 9336-CT Mouse NS0 His 9048-B7 monkey Cynomolgus Human NS0 Fc 169-CS HEK293 Fc 9326-B7 monkey ICOS Mouse Sf21 (baculovirus) Fc 168-CS Human NS0 Fc 165-B7 Human NS0 Fc 1086-PD Human HEK293 His 8206-B7 Human HEK293 His 8986-PD Mouse NS0 Fc 158-B7 B7-H2/ICOS L Mouse NS0 Fc 1021-PD Mouse NS0 His 8127-B7 Mouse NS0 His 9047-PD Cynomolgus PD-1 HEK293 His 9327-B7 monkey Cynomolgus HEK293 His 8509-PD Human NS0 Fc 1027-B3 monkey Cynomolgus B7-H3 Human NS0 His 1949-B3 HEK293 Fc 8578-PD monkey Mouse NS0 His 1397-B3 Human NS0 Fc 1224-PL B7-H3 (4Ig) Human NS0 His 2318-B3 Human HEK293 His 9075-PL Human NS0 His 6576-B7 Mouse NS0 Fc 1022-PL Human HEK293 Fc 8870-B7 PD-L2/B7-DC B7-H4 Mouse NS0 His 9107-PL Mouse NS0 Fc 4206-B7 Cynomolgus Mouse NS0 His 2154-B7 HEK293 Fc 9178-PL monkey Human NS0 Fc 7126-B7 Human NS0 His 9057-B7 B7-H5/VISTA/ PD-1H Mouse NS0 Fc 7005-B7 Cynomolgus HEK293 Fc 9408-B7 monkey Human NS0 Fc 7144-B7 Human HEK293 His 9309-B7 B7-H6 Cynomolgus HEK293 Fc 8984-B7 monkey
Learn more | rndsystems.com/proteins Butyrophilins Fc Receptors Molecule Species Source Tag Catalog # Molecule Species Source Tag Catalog #
BTN1A1/ Human NS0 His 8467-BT Mouse NS0 His 1960-FC Butyrophilin Mouse NS0 His 8540-BT Fcg RIII/CD16 Cynomolgus HEK293 His 9224-FC monkey BTN2A1 Human HEK293 His 9058-BT Human NS0 His 4325-FC BTN2A2/ Human HEK293 Fc 8918-BT Fcg RIIIA/CD16a Rat NS0 His 9596-CD Butyrophilin 2A2 Mouse NS0 His 8997-BT Fcg RIIIA/CD16a BTN3A1/CD277 Human HEK293 Fc 8539-BT Human HEK293 His 8894-FC (V176F) BTN3A2 Human CHO His 9514-BT Fcg RIIIB/CD16b Human NS0 His 1597-FC BTNL2/ Mouse NS0 His 8605-BT FcgR4/CD16-2 Mouse NS0 His 1974-CD Butyrophilin-like 2 Human NS0 His 3939-FA BTNL3/ Human CHO Fc 9658-BT Butyrophilin-like 3 FCAR/CD89 Cynomolgus NS0 His 9516-FA monkey BTNL4/ Mouse NS0 Fc 9590-BT Butyrophilin-like 4 Human NS0 His 2049-FC Mouse NS0 His 9594-BT FCRL1/FcRH1 Mouse NS0 His 7286-FC BTNL6/ Mouse CHO His 9638-BT Butyrophilin-like 6 FCRL2/FcRH2 Human NS0 His 2048-FC BTNL8/ FCRL3/FcRH3 Human NS0 His 3126-FC Human HEK293 Fc 9359-BT Butyrophilin-like 8 Human NS0 His 2078-FC Human HEK293 Fc 9659-BT FCRL5/FcRH5 BTNL9/ Mouse NS0 His 6757-FC Butyrophilin-like 9 Mouse NS0 Fc 9555-BT Human NS0 His 4705-FC FCRLB/FCRY Mouse NS0 His 4868-FC Human HEK293 His 8639-FC CD94/NKG2 Family FCRN Mouse NS0 His 6775-FC Molecule Species Source Tag Catalog # FCRN Heterodimer Mouse NS0 His 9114-FC CD94 Human CHO His 9270-CD NKG2A Mouse CHO Fc 9198-NK NKG2A/NKG2B Isoform 2 Mouse HEK293 Fc 9330-NK Killer Immunoglobulin-like Receptors (KIRs) Molecule Species Source Tag Catalog # KIR2DL1 Human NS0 Fc 1844-KR Fc Receptors KIR2DL2 Human NS0 Fc 3015-KR Molecule Species Source Tag Catalog # KIR2DL3 Human NS0 Fc 2014-KR Human NS0 His 123-FE CD23/Fce RII KIR2DL4 Human NS0 Fc 2238-KR Mouse NS0 His 6040-FE KIR2DL5 Human NS0 Fc 6634-KR Fc a/m R Human CHO His 9278-FC KIR2DS4 Human NS0 Fc 1847-KR Fce RIa Human NS0 His 6678-FC KIR3DL1 Human NS0 Fc 1225-KR Fcm R/FAIM3 Human HEK293 HA 9494-MU KIR3DL2 Human NS0 Fc 2878-KR Human NS0 His 1257-FC KIR3DS1 Human CHO Fc 4136-KR Mouse NS0 His 2074-FC Fcg RI/CD64 Rat NS0 His 9558-FC Cynomolgus HEK293 His 9239-FC Kynurenine Pathway monkey Molecule Species Source Tag Catalog # Fcg RIIA/CD32a Human NS0 His 9595-CD (H167) a-Aminoadipate Human E. coli None 7927-AT Aminotransferase Fcg RIIA/CD32a Human NS0 His 1330-CD (R167) Indoleamine Human E. coli His 6030-AO 2,3-dioxygenase/ Rat HEK293 His 9696-CD IDO Mouse E. coli His 9157-AO Fcg RIIA/CD32a Cynomolgus HEK293 His 9240-CD Sf21 monkey Kynureninase Human His 4887-KH (baculovirus) Mouse NS0 His 1460-CD Kynurenine Sf21 Rat NS0 His 9666-CD 3-Monooxygenase/ Human His 8050-KM Fcg RIIB/CD32b (baculovirus) KMO Cynomolgus HEK293 His 9246-CD monkey Tryptophan 2,3-dioxygenase/ Human E. coli His 9768-TD Fcg RIIB/C Human NS0 His 1875-CD TDO2 (CD32b/c)
Learn more | rndsystems.com/proteins LILR Family Receptors & ANGPT/ANGPTL Ligands Nectin and Nectin-like Binding Receptors Molecule Species Source Tag Catalog # Molecule Species Source Tag Catalog # Human NS0 His 923-AN Human HEK293 Fc 9360-CD Angiopoietin-1 CD96 Human NS0 His, Biotin BT923 Mouse NS0 His 5690-CD Human NS0 His 623-AN CD96v2 Human HEK293 Fc 9556-CD Angiopoietin-2 Human NS0 His, Biotin BT623B Human NS0 His 2530-CD Mouse CHO His 7186-AN Human HEK293 Fc 9174-CD Angiopoietin-like CD155/PVR Mouse NS0 Fc 9670-CD Human NS0 His 9746-AN Protein 2/ANGPTL2 Mouse NS0 His 6909-CD Human Sf21 (baculovirus) His 3829-AN Angiopoietin-like Rat HEK293 Fc 9744-CD Protein 3/ANGPTL3 Mouse Sf21 (baculovirus) His 136-AN Human NS0 Fc 1695-CR Human CHO His 4954-AN CRTAM Angiopoietin-like Mouse NS0 Fc 3687-CR Protein 3 Mouse CHO His 8344-AN Human NS0 Fc 666-DN (aa 17–220) Mouse CHO His, Biotin BT8344 Human HEK293 His 9298-DN Human NS0 His 4487-AN DNAM-1/CD226 Mouse NS0 Fc 4436-DN Angiopoietin-like Human NS0 His, Biotin BT4487 Protein 4/ANGPTL4 Cynomolgus HEK293 Fc 9276-DN Mouse CHO His 4880-AN monkey Angiopoietin-like Nectin-1 Human NS0 His 2880-N1 Protein 4 Human NS0 His 2229-N2 C-Terminal Human NS0 His 3485-AN Fragment Nectin-2/CD112 Human HEK293 Fc 9317-N2 (aa 165–406) Mouse NS0 His 3869-N2 Angiopoietin-like Protein 4 Human CHO His 8249-AN Nectin-3/CD113 Human NS0 His 3064-N3 N-Terminal Human NS0 His 2659-N4 Nectin-4 Fragment Human CHO His, Biotin BT8249 (aa 26–161) Mouse NS0 His 3116-N4 Angiopoietin-like Mouse NS0 Fc 7267-TG Human CHO His 6675-AN Protein 5/ANGPTL5 TIGIT Cynomolgus HEK293 Fc 9380-TG Angiopoietin-like monkey Human CHO c-Myc 8466-AN Protein 6/ANGPTL6 TIGIT (A103) Human CHO Fc 7898-TG Human CHO His 914-AN TIGIT (T103) Human HEK293 Fc 9464-TG Angiopoietin-like Human CHO His, Biotin BT914 Protein 7/ANGPTL7 Mouse CHO His 4960-AN LILRA1/CD85i/ SLAM Family Human NS0 His 9226-T4 LIR-6 Molecule Species Source Tag Catalog # LILRA2/CD85h/ Human HEK293 His 9040-T4 2B4/CD244/ Human NS0 Fc 1039-2B ILT1 SLAMF4 Mouse NS0 Fc 3514-2B LILRA3/CD85e Human HEK293 Fc 9517-T4 BLAME/SLAMF8 Human NS0 His 1907-BL LILRA4/CD85g/ Human NS0 His 8914-T4 ILT7 Human NS0 His 3644-CD LILRA5/CD85f/ CD48/SLAMF2 Human HEK293 Fc 9310-CD Human CHO His 8956-T4 LIR-9 Mouse NS0 His 3327-CD LILRA6/CD85b/ Human HEK293 His 9088-T4 CD58/LFA-3 Human NS0 His 1689-CD ILT8 Mouse NS0 Fc 9320-T4 Human NS0 His 1855-CD CD84/SLAMF5 LILRB1/CD85j/ Human NS0 Fc 2017-T2 Mouse NS0 His 7459-CD ILT2 Human HEK293 His 8989-T2 Human NS0 His 1898-CD CD229/SLAMF3 LILRB2/CD85d/ Human NS0 Fc 2078-T4 Mouse NS0 His 2555-CD ILT4 Human HEK293 His 8429-T4 Human CHO Fc 8235-CD CD2F-10/SLAMF9 LILRB3/CD85a/ Human HEK293 His 9159-T5 Mouse NS0 His 2829-CD ILT5 Human NS0 Fc 1806-T5 CRACC/SLAMF7 Mouse CHO His 4628-SF LILRB4/CD85k/ Human NS0 His 8488-T4 Human NS0 Fc 1908-NT ILT3 Mouse NS0 His 9095-T4 NTB-A/SLAMF6 Human HEK293 His 9299-NT LILRB5/CD85c/ Human NS0 His 8487-T4 Mouse NS0 Fc 3986-NT LIR-8 Human NS0 His 164-SL Mouse NS0 His 9288-T4 SLAM/CD150 LILRC1 Mouse NS0 His 4330-SL Rat NS0 His 9698-T4
Learn more | rndsystems.com/proteins TIM Family Receptors & Ligands TNF Superfamily Type V Subfamily Receptors & Ligands Molecule Species Source Tag Catalog # Molecule Species Source Tag Catalog # Human E. coli None 2045-GA GITR Ligand/ TNFSF18 Mouse NS0 His 2177-GL Galectin-9 Human HEK293 None 9064-GA (aa 47–173) Mouse E. coli None 3535-GA Human NS0 Fc 3388-OX Human NS0 His 1750-TM OX40/TNFRSF4 Mouse NS0 Fc 1256-OX Human HEK293 Fc 9319-TM Rat NS0 Fc 8584-OX TIM-1/KIM-1/ Mouse NS0 His 1817-TM Human NS0 His 1054-OX HAVCR Rat NS0 His 3689-TM OX40 Ligand/ Mouse NS0 His 1236-OX TNFSF4 Cynomolgus CHO Fc 9676-TM Rat NS0 His 8640-OX monkey Human NS0 Fc 2365-TM Mouse NS0 Fc 1529-TM TIM-3 TNF Superfamily Type L Subfamily Receptors & Ligands Cynomolgus HEK293 Fc 7914-TM Molecule Species Source Tag Catalog # monkey Human NS0 Fc, His 1493-CD Human NS0 His 2929-TM Mouse NS0 Fc, His 1215-CD Human HEK293 Fc 9300-TM CD40/TNFRSF5 Rat NS0 Fc 8229-CD Human HEK293 His 9407-TM TIM-4 Cynomolgus Mouse NS0 His 2826-TI HEK293 Fc 9660-CD monkey Cynomolgus HEK293 Fc 9384-TM Human HEK293 HA 6420-CL monkey CD40 Ligand/ Human E. coli His 2706-CL TNFSF5 Mouse CHO HA 8230-CL TNF Superfamily Type V Subfamily Receptors & Ligands Rat CHO HA 8414-CL Molecule Species Source Tag Catalog # CD40 Ligand/ TNFSF5 Human E. coli None 6245-CL Human NS0 Fc, His 838-4B (aa 108–261) Human CHO His 9220-4B Human NS0 Fc, His 943-D3 4-1BB/TNFRSF9/ Mouse NS0 Fc 937-4B DR3/TNFRSF25 Mouse NS0 Fc 2437-D3 CD137 Rat NS0 His 7968-4B Human NS0 Fc, His 356-HV Cynomolgus HEK293 Fc 9324-4B Mouse CHO Fc 2516-HV monkey HVEM/TNFRSF14 Cynomolgus Human E. coli His 2295-4L HEK293 Fc 9197-HV monkey 4-1BB Ligand/ Mouse NS0 His 1246-4L TNFSF9 Human NS0 His 664-LI Rat NS0 His 9188-4L LIGHT/TNFSF14 Mouse NS0 His 1794-LT Human NS0 Fc, His 382-CD Human E. coli None 1319-TL CD27/TNFRSF7 Mouse NS0 Fc 574-CD TL1A/TNFSF15 Mouse E. coli None 1896-TL Rat NS0 Fc 7888-CD
CD27 Ligand/ Human HEK293 HA 9328-CL TNFSF7 Mouse NS0 His 783-CL Human NS0 Fc, His 813-CD CD30/TNFRSF8 Human NS0 None 6126-CD Mouse NS0 Fc, His 852-CD
CD30 Ligand/ Human NS0 His 1028-CL TNFSF8 Mouse NS0 His 732-CL Human NS0 Fc 689-GR Mouse NS0 Fc, His 524-GR GITR/TNFRSF18 Rat NS0 Fc 9130-GR Cynomolgus CHO Fc 9428-GR monkey
GITR Ligand/ Human CHO HA 6987-GL TNFSF18 Human Sf21 (baculovirus) His 694-GL
Learn more | rndsystems.com/proteins V-set and Immunoglobulin domain-containing (VSIGs) Family 1.2 Molecule Species Source Tag Catalog # Human NS0 Fc 9708-VS VSIG1 1
Mouse NS0 Fc 9645-VS ) R NR VSIG2 Mouse NS0 Fc 9598-VS 4 kDa 0.8 190 Human NS0 Fc 9229-VS VSIG3 92. Mouse NS0 Fc 9367-VS 0.6 66 Human NS0 Fc 4646-VS 4 VSIG4 Mouse NS0 Fc 4674-VS 6 0.4 29 Human CHO Fc 9200-VS 21 VSIG8 (O.D. IL-2 Production 18.4 Mouse NS0 Fc 9204-VS 0.2 12.4 VSIG10 Mouse NS0 Fc 9604-VS 6. Human HEK293 His 9599-VS 0 VSIG10L 0.001 0.01 0.1 1 10 100 Human HEK293 Fc 9600-VS Recombinant Human BTN1A1 ( g/mL)
BTN1A1 Inhibits Anti-CD3-Induced IL-2 Production by Human T Cells. Human T cells were Other Related Ligands, Receptors, and Enzymes incubated with an immobilized Mouse Anti-Human CD3e Monoclonal Antibody (Catalog # MAB100; 1 µg/mL) and the indicated concentrations of Recombinant Human BTN1A1 Molecule Species Source Tag Catalog # (Catalog # 8467-BT). IL-2 secretion was measured in cell culture supernatants using the Human HEK293 His 7579-CD Human IL-2 Quantikine® ELISA Kit (Catalog # D2050). The ED for this effect is typically CD7 50 Mouse NS0 His 8145-CD 0.5–2.5 µg/mL. Recombinant Human BTN1A1 (Catalog # 8467-BT; 1 µg/lane) was assessed by SDS-PAGE analysis under reducing (R) and non-reducing (NR) conditions and Human NS0 Fc 4670-CD visualized by silver staining (inset). CD47 Human NS0 His 9396-CD Mouse NS0 Fc 1866-CD Human CHO His 6177-CD CD160 2800 Mouse CHO His 3899-CD 2600 Human NS0 Fc 2724-CD Mouse NS0 Fc 3355-CD 2400 CD200 Cynomolgus CHO Fc 9274-CD 2200 monkey Human NS0 Fc 2640-LM 2000 CD300/LMIR1 Mouse NS0 Fc 1186-LM 1800 Human NS0 His 1859-DC Dectin-1/CLEC7A (RFU) T Cell Proliferation 1600 Mouse NS0 His 1756-DC Human NS0 His 9168-SE 1400 -1 0 1 Mouse NS0 His 954-SE 10 10 10 DPPIV/CD26 VSIG-3 IgG1-Fc ( g/mL) Cynomolgus HEK293 His 9637-SE monkey VSIG-3 Inhibits Anti-CD3-induced Human CD3+ T Cell Proliferation. Human T cells were Human NS0 Fc 3384-B6 EphB6 incubated with an immobilized Mouse Anti-Human CD3e Monoclonal Antibody (Catalog # Mouse NS0 Fc 611-B6 MAB100; 1 µg/mL) and the indicated concentrations of Recombinant Human VSIG-3 Human CHO His 5668-A4 (Catalog # 9229-VS) for 72 hours. Cell proliferation was assessed by a fluorometric assay Integrin a4b1 using the redox-sensitive dye, Resazurin (Catalog # AR002). IgG-Fc controls did not alter Mouse CHO His 6054-A4 anti-CD3-induced CD3+ cell proliferation (data not shown). Integrin a4b7/ Human CHO His 5397-A3 LPAM-1 Mouse CHO His 8615-A3 Human NS0 Fc 2319-L3 LAG-3 Mouse NS0 Fc 3328-L3 Human NS0 His 2664-LR LAIR1 Mouse NS0 His 4016-LR Human CHO Fc 4546-SA Human CHO Fc, Biotin BT4546 Human CHO His 9378-SA SIRP-a Cynomolgus NS0 His 9519-SA monkey Mouse NS0 Fc 7154-SA Rat NS0 His 7307-SA Human NS0 Fc 981-TR TSLP R Mouse NS0 Fc 546-TR
Learn more | rndsystems.com/proteins Antibodies for Blocking/Neutralization or the Detection of Immuno-Oncology Targets R&D Systems offers multiple anti-mouse and anti-human antibodies for blocking/neutralization of first generation immuno-oncology targets and emerging targets. In addition, we offer a wide selection of unconjugated and fluorochrome-conjugated antibodies that are qualified for flow cytometry, immunofluorescence/immunocytochemistry, immunohistochemistry, and/or Western blot, along with antibodies that are CyTOF- ready or CyTOF-reported.
B7/CD28 Families Unconjugated Antibodies Fluorochrome-conjugated Antibodies Molecule Species Clone Catalog # (Applications) Catalog # (Applications) Human 37711 MAB140 (B/N, CyTOF-ready, E, FC, IHC) FAB140F, G, N, P, R, S, T, U, V (FC) Human Polyclonal AF140 (IHC, WB) B7-1/CD80 Mouse 111114 MAB740 (IHC, WB) Mouse Polyclonal AF740 (B/N, CyTOF-ready, E, FC, ICC/IF, WB) Human 37301 MAB141 (B/N, CyTOF-ready, FC, KO, WB) FAB141A, C, F, G, N, P, R, S, T, U, V (FC) Human Polyclonal AF-141-NA (B/N, IHC, KO, WB) B7-2/CD86 Mouse GL1 MAB741 (B/N, CyTOF-ready, FC, WB) FAB741N, P, R, S, T, U, V (FC) Mouse Polyclonal AF-441-NA (B/N, WB) Human 130021 MAB1561 (CyTOF-ready, FC, IHC) FAB1561A, C, G, N, P, R, S, T, U, V (FC) Human Polyclonal AF156 (B/N, IHC, WB) Mouse 179711 MAB1019 (WB) B7-H1/PD-L1 Mouse 929903 MAB9078 (CyTOF-ready, FC) FAB9078G, N, R, S, T, U, V (FC) Mouse 2096C MAB90781 (FC, IHC, WB) FAB90781G, N, R, S, T, U, V (FC) Mouse Polyclonal AF1019 (CyTOF-ready, FC, IHC, WB) FAB1019A, F (FC) Human 136726 MAB165 (B/N, CyTOF-ready, FC) FAB165A, C, G, N, P, R, S, T, U, V (FC) Human 136716 MAB1651 (B/N, WB) B7-H2/ICOS L Human Polyclonal AF165 (CyTOF-ready, FC, WB) Mouse 599841 MAB158 (CyTOF-ready, FC, ICC/IF) FAB158G, N, R, S, T, U, V (FC) Mouse Polyclonal AF158 (ICC/IF, WB) Human 185504 MAB1027 (CyTOF-ready, FC, KO, WB) FAB1027A, F, G, N, P, R, S, T, U, V (FC) B7-H3 Human Polyclonal AF1027 (CyTOF-ready, FC, IHC, KO, SW, WB) Mouse Polyclonal AF1397 (B/N, WB) Human 935317 MAB6576 (CyTOF-ready, FC) FAB6576N, P, R, S, T, U, V (FC) Human 973816 MAB65761 (FC, IHC) B7-H4 Mouse 297219 MAB2154 (CyTOF-ready, FC, WB) FAB2154A, G, N, R, S, T, U, V (FC) Mouse Polyclonal AF2154 (CyTOF-ready, FC, WB) Human 730804 MAB71261 (CyTOF-ready, FC, ICC/IF) FAB71261A, G, N, P, R, S, T, U, V (FC) Human Polyclonal AF7126 (CyTOF-ready, E, FC, WB) B7-H5/VISTA/PD-1H Human/Mouse 730802 Mouse 742002 MAB70051 (ICC/IF, WB) Mouse Polyclonal AF7005 (CyTOF-ready, FC, ICC/IF, WB) FAB7005A, G (FC) Human 907812 MAB80841 (B/N, ICC/IF) FAB80841R, T (FC) B7-H7/HHLA2 Human 907816 MAB8084 (ICC/IF) Human Polyclonal AF8084 (ICC/IF, WB) Human 330104 MAB3354 (WB) Human Polyclonal AF3354 (CyTOF-ready, FC, WB) FAB3354A, C (FC) BTLA Mouse 753131 MAB7600 (WB) FAB7600G (FC) Mouse Polyclonal AF3007 (WB) FAB3007G (FC) Human 37407 MAB342 (FA, WB) Human 37407R MAB342R (FA, WB) Human Polyclonal AF-342-PB (CyTOF-ready, FA, FC, ICC/IF, WB) CD28 Mouse 61109 MAB4831 (WB) Mouse 794716 MAB4832 (CyTOF-ready, FA, FC) FAB4832G, N, R, S, T, U, V (FC) Mouse Polyclonal AF483 (WB)
Learn more | rndsystems.com/antibodies B7/CD28 Families Unconjugated Antibodies Fluorochrome-conjugated Antibodies Molecule Species Clone Catalog # (Applications) Catalog # (Applications) Human 48815 MAB325 (WB) Human 922101 MAB3251 (FC) Human 2188A MAB3252 (FC, ICC/IF) FAB3252G, N, R, S, T, U, V (FC) CTLA-4 Human Polyclonal AF-386-PB (CyTOF-ready, FC, ICC/IF, WB) FAB386A, P (FC) Mouse 63828 MAB434 (B/N, CyTOF-ready, FC, WB) FAB434A, F, G, N, P, R, S, T, U, V (FC) Mouse Polyclonal AF476 (E, WB) Human 669222 MAB6975 (CyTOF-ready, FC) FAB6975A, G, N, P, R, S, T, U, V (FC) Human 669214 MAB69753 (B/N, FC) FAB69753G, N, R, S, T, U, V (FC) ICOS Human Polyclonal AF169 (IHC, WB) Mouse 670306 MAB168 (CyTOF-ready, FC) FAB168G, N, P, R, S, T, U, V (FC) Mouse Polyclonal AF168 (B/N, WB) Human 192106 MAB1086 (WB) Human 913429 MAB10861 (B/N, CyTOF-ready, FC, WB) FAB10861G, N, R, S, T, U, V (FC) PD-1 Human Polyclonal AF1086 (B/N, CyTOF-ready, E, FC, IHC, WB) FAB7115G, P (FC) Mouse 766104 MAB7738 (CyTOF-ready, FC) FAB7738G, N, P, R, S, T, U, V (FC) Mouse Polyclonal AF1021 (CyTOF-ready, FC, IHC, WB) FAB1021F, P (FC) Human 176611 MAB1224 (CyTOF-ready, FC, IHC, WB) FAB1224A, G, N, P, R, S, T, U, V (FC) Human Polyclonal AF1224 (B/N, IHC, WB) PD-L2/B7-DC Mouse 168633 MAB1022 (CyTOF-ready, FC, WB) Mouse Polyclonal AF1022 (B/N, CyTOF-ready, FC, IHC, WB) FAB1022F, G, N, P, R, S, T, U, V (FC)
Butyrophilins Unconjugated Antibodies Fluorochrome-conjugated Antibodies Molecule Species Clone Catalog # (Applications) Catalog # (Applications) Human 2151B MAB84671 (FC, ICC/IF) FAB84671G, N, R, S, T, U, V (FC) BTN1A1/Butyrophilin Mouse Polyclonal AF4765 (WB) Human Polyclonal AF8645 (IHC, WB) BTN2A2/Butyrophilin 2A2 Mouse Polyclonal AF4917 (WB) BTN3A1/CD277 Human 849203 MAB7136 (CyTOF-ready, FC) BTN3A1/2 Human Polyclonal AF7136 (WB) BTNL2/Butyrophilin-like 2 Mouse Polyclonal AF5236 (WB) BTNL8 Human 2187B MAB9359 (FC, WB) FAB9359G, N, R, S, T, U, V (FC)
CD94/NKG2 Family Unconjugated Antibodies Fluorochrome-conjugated Antibodies Molecule Species Clone Catalog # (Applications) Catalog # (Applications) Human 131412 MAB1058 (B/N, CyTOF-ready, FC) FAB1058A, G, N, P, R, S, T, U, V (FC) CD94 Human/Mouse Polyclonal AF1058 (WB) Human 131411 MAB1059 (CyTOF-ready, FC) FAB1059A, C, G, N, P, R, S, T, U, V (FC) Human 131411R MAB1059R (CyTOF-ready, FC) FAB1059RG, N, R, S, T, U, V (FC) NKG2A Mouse 705829 MAB6867 (CyTOF-ready, FC) FAB6867A, G, N, P, R, S, T, U, V (FC) Mouse 2097C MAB68671 (CyTOF-ready, FC) Human 134591 MAB138 (CyTOF-reported, FC) FAB138A, C, G, N, P, R, S, T, U, V (FC) NKG2C Human 134522 MAB1381 (CyTOF-reported, FC) FAB1381G, N, R, S, T, U, V (FC) Mouse 2098A MAB1382 (CyTOF-ready, FC) FAB1382G, N, R, S, T, U, V (FC) NKG2H Human 633810 MAB6549 (WB)
Application Key: B/N Blocking/Neutralization CyTOF-ready or CyTOF-reported Mass Cytometry E ELISA FA Functional Assay FC Flow Cytometry ICC/IF Immunocytochemistry/Immunofluorescence IHC Immunohistochemistry KO Knockout SW Simple Western WB Western Blot Fluorochrome Key for FAB/IC Catalog Numbers Ending In: A: Allophycocyanin; C: PerCP; F: Fluorescein; G: Alexa Fluor® 488; N: Alexa Fluor® 700; P: Phycoerythrin; R: Alexa Fluor® 647; S: Alexa Fluor® 750; T: Alexa Fluor® 594; U: Alexa Fluor® 350; V: Alexa Fluor® 405 Learn more | rndsystems.com/antibodies Fc Receptors Unconjugated Antibodies Fluorochrome-conjugated Antibodies Molecule Species Clone Catalog # (Applications) Catalog # (Applications) Human 138628 MAB123 (B/N, CyTOF-ready, FC, WB) FAB123G, N, R, S, T, U, V (FC) CD23/Fce RII Human Polyclonal AF123 (B/N, ICC/IF, WB) Mouse 691632 MAB6900 (CyTOF-ready, FC) FAB6900G, N, R, S, T, U, V (FC) Human 773704 MAB6678 (B/N, CyTOF-ready, FC) FAB6678A, C, G, N, R, S, T, U, V (FC) Fce RIa Human Polyclonal AF6678 (CyTOF-ready, FC) Human 276426 MAB12571 (CyTOF-ready, FC, WB) FAB12571C, F, G, N, P, R, S, T, U, V (FC) Human 22 MAB12572 (CyTOF-ready, FC) FAB12572F, G, N, P, R, S, T, U, V (FC) Human 32.2-1A MAB12573 (CyTOF-ready, FC) FAB12573G, N, P, R, S, T, U, V (FC) Human 10.1 MAB1257 (CyTOF-ready, FC, ICC/IF) FAB1257G, N, R, S, T, U, V (FC) Fcg RI/CD64 Human Polyclonal AF1257 (B/N, WB) Mouse 290322 MAB20741 (CyTOF-ready, FC) FAB20741A, C, G, N, P, R, S, T, U, V (FC) Mouse 290305 MAB2074 (WB) Mouse Polyclonal AF2074 (WB) Human 190723 MAB1330 (CyTOF-ready, FC, WB) FAB1330A, G, N, P, R, S, T, U, V (FC) Fcg RII/CD32 Human Polyclonal AF1330 (B/N, CyTOF-ready, FC, ICC/IF, WB) Fcg RIIA/CD32a Human Polyclonal AF1875 (B/N, CyTOF-ready, FC, WB) Fcg RIIB/CD32b Mouse 190907 MAB14601 (E, WB) Mouse 190909 MAB1460 (CyTOF-ready, FC, WB) FAB1460F, G, N, R, S, T, U, V (FC) Fcg RII/RIII (CD32/CD16) Mouse Polyclonal AF1460 (ICC/IF, WB) Human 245536 MAB2546 (CyTOF-ready, FC) FAB2546A, C, F, G, N, P, R, S, T, U, V (FC) Human Polyclonal AF1597 (B/N, WB) Fcg RIII/CD16 Mouse 275024 MAB1960 (WB) Mouse 275003 MAB19601 (CyTOF-ready, FC) FAB19601A, C, F, G, N, P, R, S, T, U, V (FC) Mouse Polyclonal AF1960 (B/N, ICC/IF, WB) Fcg RIIIB/CD16b Human 245514 MAB1597 (CyTOF-ready, FC, WB) FAB1597G, N, R, S, T, U, V (FC) Human 488032 MAB3939 (CyTOF-ready, FC) FAB3939A, F, G, N, P, R, S, T, U, V (FC) FCAR/CD89 Human Polyclonal AF3939 (CyTOF-ready, FC, WB) Human 282415 MAB2049 (CyTOF-ready, FC, WB) FAB2049A, G, N, P, R, S, T, U, V (FC) Human 282420 MAB20491 (WB) FCRL1/FcRH1 Human Polyclonal AF2049 (WB) Mouse 745916 MAB7286 (CyTOF-ready, FC) FAB7286G, N, R, S, T, U, V (FC) Mouse Polyclonal AF7286 (CyTOF-ready, FC) Human 296902 MAB2048 (CyTOF-ready, FC, WB) FAB2048A, G, N, P, R, S, T, U, V (FC) FCRL2/FcRH2 Human Polyclonal AF2048 (FC, WB) Human 546828 MAB3126 (CyTOF-ready, FC) FAB3126A, G, N, P, R, S, T, U, V (FC) FCRL3/FcRH3 Human Polyclonal AF3126 (CyTOF-ready, FC) Human 307314 MAB2087 (WB) FCRL5/FcRH5 Human Polyclonal AF2087 (CyTOF-ready, FC, WB) Mouse Polyclonal AF6757 (CyTOF-ready, FC) FAB6757A, G (FC) Human 454217 MAB4705 (FC, WB) IC4705G, N, R, S, T, U, V (FC) FCRLB/FCRY Human Polyclonal AF4705 (WB) Mouse 465905 MAB4868 (WB) Human 937508 MAB8639 (CyTOF-ready, FC, WB) IC8639G, N, S, T, U, V (FC) FCRN Mouse Polyclonal AF6775 (CyTOF-ready, FC, WB)
Application Key: B/N Blocking/Neutralization CyTOF-ready or CyTOF-reported Mass Cytometry E ELISA FA Functional Assay FC Flow Cytometry ICC/IF Immunocytochemistry/Immunofluorescence IHC Immunohistochemistry KO Knockout SW Simple Western WB Western Blot Fluorochrome Key for FAB/IC Catalog Numbers Ending In: A: Allophycocyanin; C: PerCP; F: Fluorescein; G: Alexa Fluor® 488; N: Alexa Fluor® 700; P: Phycoerythrin; R: Alexa Fluor® 647; S: Alexa Fluor® 750; T: Alexa Fluor® 594; U: Alexa Fluor® 350; V: Alexa Fluor® 405 Learn more | rndsystems.com/antibodies Killer Immunoglobulin-like Receptors (KIRs) Unconjugated Antibodies Fluorochrome-conjugated Antibodies Molecule Species Clone Catalog # (Applications) Catalog # (Applications) KIR pan/CD158 Human 180704 MAB1848 (CyTOF-ready, FC) FAB1848A, F, G, N, P, R, S, T, U, V (FC) KIR2DL1/KIR2DS5 Human 143211 MAB1844 (CyTOF-ready, FC) FAB1844A, C, F, G, N, P, R, S, T, U, V (FC) KIR2DL3/CD158b2 Human 180701 MAB2014 (CyTOF-reported, FC) FAB2014A, F, G, N, P, R, S, T, U, V (FC) KIR2DL4/CD158d Human 181703 MAB2238 (CyTOF-reported, FA, FC) FAB2238A, F, G, N, P, R, S, T, U, V (FC) KIR2DS1/CD158h Human 1127B MAB8887 (FC) FAB8887G, N, P, R, S, T, U, V (FC) KIR2DS4/CD158i Human 179315 MAB1847 (CyTOF-ready, FC, WB) FAB1847A, G, N, P, R, S, T, U, V (FC) KIR2DS5/CD158g Human 1165A MAB8920 (FC) FAB8920G, N, R, S, T, U, V (FC) Human DX9 MAB1225 (B/N, CyTOF-reported, FC) FAB1225A, G, N, R, S, T, U, V (FC) KIR3DL1 Human 177407 MAB12251 (CyTOF-ready, FC) FAB12251A, F, G, N, P, R, S, T, U, V (FC) KIR3DL2/CD158k Human 539304 MAB2878 (CyTOF-ready, FC) FAB2878A, C, G, N, P, R, S, T, U, V (FC) KIR3DL3/CD158z Human 1136B MAB8919 (FC) FAB8919G, N, R, S, T, U, V (FC)
Kynurenine Pathway Unconjugated Antibodies Fluorochrome-conjugated Antibodies Molecule Species Clone Catalog # (Applications) Catalog # (Applications) a-Aminoadipate Aminotransfer- Human Polyclonal AF7927 (WB) ase Indoleamine 2,3-dioxygenase/ Human 700838 MAB6030 (CyTOF-ready, FC, ICC/IF) IC6030A, C, G, P, R, S, T, U, V (FC) IDO Human 589731 MAB4887 (WB) Human Polyclonal AF4887 (IP, WB) Kynureninase Mouse 771312 MAB7389 (IHC, WB) Mouse/Rat Polyclonal AF7389 (WB) Tryptophan Hydroxylase Pan Human Polyclonal PPS038 (IHC, WB) Specific Human Polyclonal AF5276 (IHC, WB) Tryptophan Hydroxylase 1/TPH-1 Human 508417 MAB5276 (IP, WB) Phospho-Tryptophan Hydroxylase Multi-species Polyclonal PPS039 (WB) 1/TPH-1 (S58) Phospho-Tryptophan Hydroxylase Multi-species Polyclonal PPS063 (WB) 1/TPH-1 (S260)
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