
( (51) International Patent Classification: Published: A61P 35/00 (2006.01) G01N 33/50 (2006.01) — with international search report (Art. 21(3)) G16H 50/20 (2018.01) A61K 39/00 (2006.01) G16H 50/30 (2018.01) (21) International Application Number: PCT/US20 19/058578 (22) International Filing Date: 29 October 2019 (29. 10.2019) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/752,288 29 October 2018 (29. 10.2018) US 62/788,3 13 04 January 2019 (04.01.2019) US 62/855,332 31 May 2019 (3 1.05.2019) US (71) Applicant: GENOCEA BIOSCIENCES, INC. [US/US]; Cambridge Discovery Park, 100 Acorn Park Drive, 5th Floor, Cambridge, Massachusetts 02140 (US). (72) Inventors: FLECHTNER, Jessica Baker; 1 Briant Drive, Sudbury, Massachusetts 01776 (US). DOBSON, Jason R.; 44 Pole Plain Road, Sharon, Massachusetts 02067 (US). (74) Agent: DAUKSS, Dana M. et al.; Choate, Hall & Ste¬ wart LLP, Two International Place, Boston, Massachusetts 021 10 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(H)) (54) Title: TREATMENT METHODS (57) Abstract: Methods and compositions for identifying tumor antigens of human lymphocytes, and for identifying subjects for cancer therapy, are provided herein. TREATMENT METHODS CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No. 62/752,288, filed October 29, 2018, U.S. Provisional Application No. 62/788,313, filed January 4, 2019, and U.S. Provisional Application No. 62/855,332, filed May 31, 2019, the contents of each of which are hereby incorporated by reference herein in their entirety. BACKGROUND [0002] Cancer is characterized by proliferation of abnormal cells. Many treatments include costly and painful surgeries and chemotherapies. Although there is a growing interest in cancer therapies that target cancerous cells using a patient’s own immune system, such therapies have had limited success. SUMMARY [0003] The present invention features, inter alia, methods of identifying and/or selecting a cancer subject for initiation, continuation, modification, and/or discontinuation of a cancer therapy. [0004] Accordingly, one aspect of the disclosure featues a method of identifying a subject as a candidate for cancer therapy, the method comprising a) obtaining, providing, or generating a library comprising bacterial cells or beads comprising a plurality of tumor antigens, wherein each bacterial cell or bead of the library comprises a different tumor antigen; b) contacting the bacterial cells or beads with antigen presenting cells (APCs) from the subject, wherein the APCs internalize the bacterial cells or beads; c) contacting the APCs with lymphocytes from the subject, under conditions suitable for activation of lymphocytes by a tumor antigen presented by one or more APCs; d) determining whether one or more lymphocytes are activated by, or not responsive to, one or more tumor antigens presented by one or more APCs, e.g., by assessing (e.g, detecting or measuring) a level (e.g, an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; e) identifying one or more tumor antigens as a stimulatory antigen and/or an inhibitory antigen; and f) generating a ratio of the number of stimulatory antigens to inhibitory antigens that represents the subject response profile; and g) comparing the subject response profile to a target response profile to select the subject as a candidate subject for initiation, continuation, modification, discontinuation or non initiation of a cancer therapy. [0005] In some embodiments, the method further comprises generating the target response profile by a method comprising h) contacting the bacterial cells or beads with antigen presenting cells (APCs) from a target subject, wherein the APCs internalize the bacterial cells or beads; i) contacting the APCs with lymphocytes from the target subject, under conditions suitable for activation of lymphocytes by a tumor antigen presented by one or more APCs; j) determining whether one or more lymphocytes are activated by, or not responsive to, one or more tumor antigens presented by one or more APCs, e.g., by assessing (e.g, detecting or measuring) a level (e.g, an increased or decreased level, relative to a control), of expression and/or secretion of one or more immune mediators; k) identifying one or more tumor antigens as a stimulatory antigen and/or inhibitory antigen; and 1) generating a ratio of the number of stimulatory antigens to inhibitory antigens that represents the target response profile. [0006] In some embodiments the target response profile is from one or more target subjects who exhibit or previously exhibited at least one beneficial response to cancer. In some embodiments, the target response profile comprises a ratio of the number of stimulatory antigens to the number of inhibitory antigens that is at least 100:1, 50:1, 20:1, 10:1, 5:1, 2:1, 1.5:1, 1.4:1, 1.2:1, 1.1:1 0.9:1, 0.8:1, 0.7:1, 0.6:1, or 0.5:1. In some embodiments the beneficial response comprises a positive clinical response to a cancer therapy or combination of therapies. In some embodiments, the beneficial response comprises a spontaneous response to a cancer. In some embodiments, the beneficial response comprises clearance of a cancer, e.g., a level of one or more clinical measures associated with clearance of a cancer. In some embodiments, the beneficial response comprises a lack of a relapse, recurrence, and/or metastasis of a cancer, e.g., over a defined period of time (e.g, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 weeks, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 years). In some embodiments, the beneficial response comprises a positive cancer prognosis. In some embodiments, the beneficial response comprises a lack of one or more toxic responses and/or side effects (e.g., one or more measurable toxic responses or side effects) to a cancer therapy or combination of therapies. [0007] In some embodiments, the target response profile is from one or more target subjects who exhibit or previously exhibited one or more deleterious and/or non-beneficial response to cancer. In some embodiments, the target response profile comprises a ratio of the number of stimulatory antigens to the number of inhibitory antigens that is less than 5:1, 2:1, 1.5:1, 1.4:1, 1.2:1, 1.1:1 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.25:1, 0.125:1, 0.01:1, or 0.001:1. In some embodiments, the deleterious and/or non-beneficial response comprises a negative clinical response and/or a failure to respond, to a cancer therapy or combination of therapies. In some embodiments, the deleterious and/or non-beneficial response comprises a lack of clearance of a cancer, e.g., a level of one or more clinical measures associated with lack of clearance of a cancer. In some embodiments, the deleterious and/or non-beneficial response comprises at least one relapse, recurrence, and/or metastasis of a cancer. In some embodiments, the deleterious and/or non-beneficial response comprises a negative cancer prognosis. In some embodiments, the deleterious and/or non-beneficial response comprises one or more toxic responses and/or side effects (e.g, one or more measurable toxic responses and/or side effects) to a cancer therapy or combination of therapies. [0008] In some embodiments, the method further comprises selecting the candidate subject for initiation of a cancer therapy or combination of cancer therapies. In some embodiments, the method further comprises selecting the candidate subject for continuation of a cancer therapy or combination of cancer therapies. In some embodiments, the method further comprises selecting the subject as a candidate subject if the subject response profile comprises ratio of the number of stimulatory antigens to the number of inhibitory antigens that is at least 100: 1, 50: 1, 20: 1, 10:1, 5:1, 2:1, 1.5:1, 1.4:1, 1.2:1, 1.1:1 0.9:1, 0.8:1, 0.7:1, 0.6:1, or 0.5:1.
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