DOCSLIB.ORG

Gene Therapy Turns 30 Years Old the Dermatology Branch At

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gene Therapy Turns 30 Years Old the Dermatology Branch At NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 27 ISSUE 3 • MAY-JUNE 2019 Gene Therapy Turns The Dermatology Branch at NIH 30 Years Old Research, Colleagues, and a Shift from NCI to NIAMS An NIH First That Almost Didn’t BY MOHOR SENGUPTA, NEI, AND LAURA STEPHENSON CARTER, OD Happen BY CHRISTOPHER WANJEK, OD When STEVEN ROSENBERG reviewed a draft email-blast message advertising his upcoming keynote address at a May 9, 2019, meeting at the University of Pennsylvania, he was struck by the final paragraph: “This symposium comes at a historic time. Thirty years ago this May, ISAAC BROWNELL AND LINGLING MIAO, NIAMS Dr. Rosenberg and colleagues shepherded in the era of gene therapy when they removed, genetically altered, and returned cells to a patient with malignant melanoma.” “This is not the kind of thing I keep track of, these historic events,” said Rosenberg, who as long-serving chief of the National Cancer Institute (NCI) Surgery Branch was the first to insert foreign genes into a human. “I’m too busy keeping track Merkel cells (green) are clustered in touch-sensitive areas called touch domes. Shown: Neonatal mouse touch dome. of today’s events.” Nevertheless, he pulled out a set of In Spring 1975, desperate parents brought their six-year-old daughter to handwritten notes in faded pencil and the NIH Dermatology Branch to be treated for a rare, chronic skin disease—coupled with ink, circa 1990, listing the dates of the arthritis—that had plagued her for more than four years and was making her miserable. unprecedented 16 reviews needed to perform Her doctors “were at the end of the line in terms of what to do,” said Stephen Katz in the world’s first gene-therapy experiment a 2018 oral-history interview. He was a senior investigator in 1975 and had joined the on a human. Next came a copy of the Dermatology Branch, which was then part of the National Cancer Institute (NCI), only 1990 paper in the New England Journal of the year before. “She had been treated with everything.” He biopsied some of the affected Medicine (N Engl J Med 323:570–578, 1990) CONTINUED ON PAGE 12 describing the 1989 experiments, along with Rosenberg’s own printed list of historic NIH CONTENTS “firsts” around this period. FEATURES • |1| Gene Therapy Turns 30 Years Old |1| Dermatology Branch at NIH |6,7| NINDS Then he rattled off names of colleagues Scientific Directors: New and Former|9| DeMystifying Medicine: From Deep Sea Vents to Our and descriptions of patient volunteers as if Own Stomachs |11| My Room, Your Room the historic events transpired yesterday. DEPARTMENTS • |2| DDIR: Equity and Diversity |3| The SIG Beat |4| Training Page: Do-It- CONTINUED ON PAGE 10 Yourself Training |5| News You Can Use: Technology Transfer |7| Abbreviations |8| Research Briefs |16| Colleagues: Recently Tenured |20| Photographic Moment: Giant MRI FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH Equity and Diversity in the NIH Intramural Research Program BY MICHAEL GOTTESMAN, DDIR, AND GISELA STORZ, CHAIR, NIH EQUITY COMMITTEE How can equity and diversity in investigator-selection process that would October 2018 the NEC submitted a the NIH intramural research program ensure diversity; equity and inclusion document to the DDIR with four main (IRP) continue to be improved? The goals; and recommendations for how the recommendations: NIH Equity Committee (NEC) was NEC and the Chief Officer for Scientific 1. Each IC must clearly define the established in November 2017 to help Workforce Diversity can help the IC duties and expectations of lab and branch address this question. Modeled on the achieve those goals. chiefs (or their equivalents). Central Tenure Committee, the NEC At the meeting with the NEC, the SD 2. The effectiveness of all lab and comprises 20 members—18 senior gives a presentation about the informa- branch chiefs (or their equivalents) must scientists and two scientific directors tion provided. Two committee members be evaluated every four years by the BSCs. (SDs)—representing almost all insti- serve as primary reviewers and prepare a (Although the BSCs now evaluate the tutes and centers (ICs). As quality of intramural research its first task, the committee at least every four years, they has been meeting with the One striking trend is the under- don’t always evaluate the lead- SDs from each IC to learn representation of certain groups in ership effectiveness of the lab about the demographics and and branch chiefs.) resource distribution in their biomedical research . in leadership 3. Lab and branch chiefs intramural programs. positions. should remain in their posi- In advance of each meeting, tions for no more than three the SD—often with the help four-year BSC review cycles of the clinical director (CD) (plus time prior to the initial report that the NEC chair presents at a for that IC—provides de-identified review and up to two years after the joint meeting of the SDs and CDs. The information about the IC’s tenure-track third cycle of positive reviews), except in reports are constructed to share each IC’s scientists, tenured scientists, senior extraordinary circumstances. This recom- best practices as well as identify areas that scientists, and senior clinicians. The SD mendation assumes that the BSC reviews need attention. To date, the NEC has also provides an organizational chart are positive; if any of the reviews are nega- evaluated the intramural programs of 12 showing the demographics of the IRP tive, it’s anticipated that the turnover of ICs. The SDs have indicated that review- leadership and a written summary that lab and branch chiefs would happen more ing these data and getting feedback from comments on the data and addresses the quickly. the NEC has been a valuable experience. hiring procedures, review practices, and 4. Leadership appointments must The presentations have been high- selection process for ad hoc Board of occur through open and transparent lighting trends across the IRP. One strik- Scientific Counselors (BSC) members. processes. ing trend is the under-representation of [The Deputy Director for Intramural certain groups in biomedical research— Research (DDIR) and NIH Committee The NEC’s recommendations— women, Asian Americans, and others—in Management approve the members of the with input from the SDs, CDs, and leadership positions. The presentations main BSC and ensure diversity; the ad NIH senior leadership—have now been also highlight extremely long tenures hoc members are chosen by the ICs]. The converted into policy. Discussions are for some lab and branch chiefs (or their summary also specifies how discretionary still ongoing about how this policy will equivalents). funding is awarded to investigators and be implemented. For example, one new Given that a dynamic organization includes proposed corrections to the policy will be that current lab and branch thrives on diversity and new ideas, in 2 THE NIH CATALYST MAY-JUNE 2019 THE SIG BEAT NEWS FROM AND ABOUT THE SCIENTIFIC INTEREST GROUPS is to generate innovative approaches in the field of digital pathology through artificial- intelligence tools. For more information HOUSSEIN A. SATER, NCI about the MxIF SIG and instructions for how to join the LISTSERV mailing list, contact the group chair and advisor: Houssein A. Sater (houssein.abdulsater@ chiefs whose service exceeds the three nih.gov). cycles of BSC review will be expected to step down within two years after the A multiplex spectrally unmixed immunofluorescence image of a lung-cancer tissue stained with seven biomarkers. New SIG: Epilepsy next BSC review of their lab or branch. Each IC is expected to have a completed The Epilepsy Scientific Interest plan by January 2020. Each SD will pres- New SIG: Multiplex Immuno- Group (SIG) brings together investigators, ent their implementation plans to both fluorescence clinicians, and researchers who are inter- the DDIR and NEC in the coming year. ested in epilepsy and in understanding its Intramural and extramural scien- Other trends are also being noted pathophysiology and the effects of treat- tists who are using multiplex immuno- by the NEC. As a result of the frequent ment on neural function and connectivity. histochemistry and immunofluorescence comment that many potential tenure-track Epilepsy studies at NIH take place in sev- technologies to study complex tissue struc- candidates are not even aware of the tre- eral institutes including NINDS, NIMH, tures (such as tumor microenvironments) mendous benefits of working in the IRP, and NICHD. NIH intramural researchers can share their knowledge via the Multi- the NEC recommended that a “Rising are using structural and functional imag- plex Immunofluorescence (MxIF) SIG. Stars” seminar program be developed: ing before and after surgical resection; These technologies are used to identify the Extramural junior scientists who are doing investigating how surgical resection on presence of multiple biological markers in exciting research will be invited to give regions of the human cortex affect neural a single tissue sample or different samples. seminars at NIH. This recognition will plasticity and cognitive function; explor- The methodology can be an invaluable tool allow IC investigators to become familiar ing intraoperative and long-term record- for tumor-tissue immune-profiling and as a with the work of the Rising Stars, who will ings of neural activity that are routinely way to identify multiple treatment targets in turn learn about the IRP. The NEC was acquired in the course of treatment; and in the same tissue section. This approach encouraged by the very large response to evaluating human brain tissue samples to requires critical thinking and bioinformatic the first call for nominations. Look for understand the physiology and molecular tools for effective segmentation, algorithm “Rising Star” talks in the coming months. and genetic pathways in both normal and building, and advanced spatial analysis.
Load more

Recommended publications
  • THERAPEUTIC FOCUS Oncology Immunotherapy Is an Emerging Powerhouse in Cancer Treatment
    THERAPEUTIC FOCUS Oncology Immunotherapy is an emerging powerhouse in cancer treatment. Early gains being made in multiple tumor types provide a glimpse of the effectiveness of several agents and regimens. While longer follow-up is needed, the results have analysts talking about a big shift in the war on cancer. Joe Dysart reports hile results are preliminary, continued head-turning advanc- 60% of all cancers in the developed world within the next decade, es in cancer treatment using immunotherapy have many according to a report released by Citigroup last summer, “Immu- Wdrug makers in oncology wondering: have we turned the notherapy: The Beginning of the End for Cancer.” corner on the war on cancer? Research released earlier this summer Stephanie Hawthorne, PhD, senior director, Kantar Health, indicates that immunotherapy—once perceived as an interest- sees similar prospects: “We will likely see these immunotherapies ing treatment for a handful of cancer tumors—may be effective expand beyond the few tumors in which they will initially launch, against a much wider range of cancers. Moreover, the research is and eventually penetrate nearly all solid tumors and even some being greeted by an eager FDA, which a few years back created hematologic indications,” she tells MM&M. “In general, in the a fast-track approval program—known as Breakthrough Therapy metastatic setting, I can see these drugs being used in 50% to 60% designation—to bring drugs that treat life-threatening diseases to of patients at some time during the course of their disease.”
    [Show full text]
  • Vince Devita: the View from the Top
    Masterpiece Vince DeVita: the view from the top ➜ Interview by Chistine Haran As director of the NCI between 1980 and 1988, Vince DeVita was a Commander in Chief of America’s War on Cancer. He has little time for those who now criticise the plan of attack – or the outcome. But he warns that if we are to win the battles in the molecular arena, we will need to fight on an altogether grander scale. Disillusionment with the speed of Did the War on Cancer succeed? progress in finding a cure for cancer VINCE DEVITA You hear and read that the War has led some people to question the on Cancer failed, but actually it did everything it vision of the 1971 National Cancer Act was supposed to do. It supported basic research and the way it was interpreted as some handsomely. It has now spent about $50 billion sort of quasi-military campaign. Did on research, of which 80% has gone into basic you get it right? research. It set up applications programmes – VINCE DEVITA We had a very straightforward the EORTC [European Organisation for mandate to support basic research and the Research and Treatment of Cancer] and US application of the results of the research to clinical trials programmes. And what’s happened reduce the incidence and the morbidity and to the incidence and morbidity and mortality of mortality from cancer. cancer? The incidence of cancer in this country Period. End of story. What was so controversial started dropping in 1990 and has continued to about it? The National Institutes of Health drop every year since, and so has mortality.
    [Show full text]
  • Historical Overview of Immunotherapy
    Historical overview of immunotherapy Before introduction of immune checkpoint inhibitors John B.A.G. Haanen, MD PhD ESMO ASIA IO preceptorship Nov 2018 My disclosures • I have provided consultation, attended advisory boards, and/or provided lectures for: Pfizer, Bayer, MSD, BMS, IPSEN, Novartis, Roche/Genentech, Neon Therapeutics, Celsius Therapeutics, Gadeta BV, Immunocore, Seattle genetics for which NKI received honoraria • Through my work NKI received grant support from BMS, MSD, Novartis and Neon Therapeutics Historical background examples of immunotherapy and their impact on survival • Coley’s toxine and spin-off • Allogeneic bone marrow and peripheral stem cell transplantations – Hematological malignancies – (Solid tumors) • High dose interleukin-2 and LAK cell therapy – Metastatic melanoma – Metastatic clear cell renal cell cancer • Adoptive cell therapy with TIL History of cancer immunotherapy Virchow: Burnet: Rosenberg: Bendani: Immune Immune- IL-2 and Maloney: Anti-idiotype infiltrates surveillance LAK cells Rituximab vaccination 1863 1898 1957 1976 1985 1992 1995 1998 1999 Coley‘s Morales: Lejeune: Slaman: toxin BCG Isolated limb Trastuzumab perfusion Courtesy of R. Stahel Coley’s toxin Complete remission of a sarcoma in a patient after 2 episodes of erysipelas caused by streptococcus pyogenes William Coley, 1893 Courtesy of R. Stahel Coley’s toxin • Induction of erysipelas by direct inoculation with streptococci • Coley’s toxin: Heat inactivated mixture of streptoccoci and serratia About 900 patients treated, most inoperable
    [Show full text]
  • Bringing Til Therapy Beyond Melanoma: Advancing the Treatment of Advanced Pancreatic and Ovarian Cancers
    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 8-2020 BRINGING TIL THERAPY BEYOND MELANOMA: ADVANCING THE TREATMENT OF ADVANCED PANCREATIC AND OVARIAN CANCERS Donald Sakellariou-Thompson Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Immunotherapy Commons, and the Medicine and Health Sciences Commons Recommended Citation Sakellariou-Thompson, Donald, "BRINGING TIL THERAPY BEYOND MELANOMA: ADVANCING THE TREATMENT OF ADVANCED PANCREATIC AND OVARIAN CANCERS" (2020). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 1022. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1022 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. BRINGING TIL THERAPY BEYOND MELANOMA: ADVANCING THE TREATMENT OF ADVANCED PANCREATIC AND OVARIAN CANCERS by Donald Anastas Sakellariou-Thompson, B.S. APPROVED: ______________________________ Chantale Bernatchez, Ph.D. Co-Advisory Professor ______________________________ Patrick Hwu, M.D. Co-Advisory Professor _____________________________ Gregory Lizee, Ph.D. ______________________________ Carlos Antonio Torres-Cabala, M.D. ______________________________ Gheath Al-Atrash, D.O. ______________________________ Roza Nurieva, Ph.D.
    [Show full text]
  • Challenges and Next Steps in the Advancement of Immunotherapy: Summary of the 2018 and 2020 National Cancer Institute Workshops
    Open access Short report J Immunother Cancer: first published as 10.1136/jitc-2021-003048 on 15 July 2021. Downloaded from Challenges and next steps in the advancement of immunotherapy: summary of the 2018 and 2020 National Cancer Institute workshops on cell- based immunotherapy for solid tumors Laura K Fogli,1 Rosemarie Aurigemma,2 Connie L Sommers,1 Anju Singh,1 1 1 Kasia Bourcier, Marc S Ernstoff , on Behalf of the NCI Cell Therapy Workshop Committee To cite: Fogli LK, ABSTRACT cell therapies, including vectors and reagents, and provide Aurigemma R, Sommers CL, Cell- based immunotherapies have had remarkable training programs for technical staff; and 4) develop and et al. Challenges and next success in the clinic, specifically in the treatment of share standard operating procedures for cell handling steps in the advancement of hematologic malignancies. However, these strategies and analytical assays, and work with the Food and Drug immunotherapy: summary of Administration to harmonize product characterization the 2018 and 2020 National have had limited efficacy in patients with solid tumors. To specifications. Cancer Institute workshops better understand the challenges involved, the National on cell- based immunotherapy Cancer Institute (NCI) convened an initial workshop with for solid tumors. Journal for immuno- oncology thought leaders in December 2018 ImmunoTherapy of Cancer and a follow- up workshop in December 2020. The goals INTRODUCTION 2021;9:e003048. doi:10.1136/ of the NCI workshops on cell- based immunotherapy for The expanded knowledge of the immune jitc-2021-003048 solid tumors were to discuss the current state of the field system over the past half century, coupled of cell- based immunotherapy, obtain insights into critical with advances in cellular and molecular tech- ► Additional supplemental knowledge gaps, and identify ways in which NCI could nologies, has led to a revolution in immuno- material is published online only.
    [Show full text]
  • Research Fellowships in Surgical Oncology and Cancer Immunotherapy
    RESEARCH FELLOWSHIPS IN SURGICAL ONCOLOGY AND CANCER IMMUNOTHERAPY National Cancer Institute • National Institutes of Health The Research Fellowships in Surgical Oncology and Cancer Immunotherapy at the National Cancer Institute encompass two time-honored programs combining bench research in Surgical Oncology with training in clinical research through direct patient care. The unique environment of the Clinical Center at the National Institutes of Health allows for direct bench-to-bedside and bedside-to-bench translational research under the direction of world leaders in Surgical Oncology. Two and three year research programs are available. The The National Cancer NIH Clinical Institute Research Center The National Cancer Institute (NCI) is one of the 27 The Clinical Center at the National Institutes of Health medical research institutes that form the association of is a comprehensive hospital providing both inpatient and the National Institutes of Health. Dedicated to the study outpatient care, free of cost, to patients participating in and treatment of malignancies, the various branches of NIH clinical research protocols. From the surgical the NCI research and provide care for a broad spectrum of perspective, this allows Research Fellows direct access cancers. The Thoracic and Oncologic Surgery Branch to patient tissue for scientific study as well as the (TOSB) and the Surgery Branch (SB) are jointly opportunity to participate directly in clinical protocols responsible for the study and clinical care of cancers and administer direct patient care. The unique profile of traditionally managed by Surgical Oncologists and rare pathologies treated at the Clinical Center provides Thoracic Surgeons. These two divisions direct the exposure to and expertise in conditions unlikely to be Fellowships in Surgical Oncology and Cancer encountered elsewhere with regularity.
    [Show full text]
  • 2011 MRA Retreat Agenda
    AGENDA Mayflower Renaissance Hotel 1127 Connecticut Avenue, NW, Washington, DC Wednesday, February 16th 6:30-8:00 pm Opening Reception Welcome: Debra Black, MRA Co-Founder and Chair of the Board Thursday, February 17th 8:00-8:15 Opening Remarks: Wendy K.D. Selig, MRA President and CEO 8:15-11:25 Genetic Basis for Melanoma Prevention, Prognostics, and Therapy Chair: David E. Fisher 8:15-8:40 Identification of novel melanoma risk genes using high-throughput genomics - Kevin Brown, National Cancer Institute 8:40-9:05 Transcriptome sequencing to detect gene fusions in melanoma - Nallasivam Palanisamy, University of Michigan 9:05-9:30 Insights from sequencing the melanoma transcriptome and exome - Ruth Halaban, Yale University 9:30-9:55 Targeting insulin receptor substrates for destruction as a therapeutic modality for treating melanoma - Alexander Levitzki, Hebrew University of Jerusalem 9:55-10:10 Break 10:10-10:35 Pro-invasion metastasis drivers in early stage melanoma are oncogenes - Lynda Chin, Dana-Farber Cancer Institute 10:35-11:00 Sulforaphane, a melanoma prevention agent for high-risk MC1R genotypes - Sancy Leachman, University of Utah 11:00-11:25 Targeted strategies for melanoma treatment and prevention - David E. Fisher, Massachusetts General Hospital 11:45-1:00 Lunch Keynote address: Michael Milken, MRA Board Member 1:00-1:30 NIH as a Partner in Advancing Melanoma Research Douglas R. Lowy, Deputy Director, National Cancer Institute 1:30-2:30 MRA Young Investigators Chair: Padmanee Sharma, University of Texas MD Anderson Cancer
    [Show full text]
  • Department of Health and Human Services Public Health Service National Cancer Institute
    DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE NATIONAL CANCER INSTITUTE 120th NATIONAL CANCER ADVISORY BOARD Summary of Meeting December 4-5, 2001 Building 31C, Conference Room 10 National Institutes of Health Bethesda, Maryland 120th National Cancer Advisory Board NATIONAL CANCER ADVISORY BOARD BETHESDA, MARYLAND Summary of Meeting December 4-5, 2001 The National Cancer Advisory Board (NCAB) convened for its 120th regular meeting on Tuesday, December 4, in Conference Room 10 of Building 31, National Institutes of Health (NIH), Bethesda, MD. The meeting was open to the public on Tuesday, December 4, 2001, from 8:45 a.m. to 4:00 p.m. The meeting was closed to the public from 4:15 p.m. until adjournment at 5:00 p.m. The meeting was reopened to the public on Wednesday, December 5, 2001, at 8:30 a.m. until adjournment at 12:00 noon. Dr. Larry Norton, Director, Medical Breast Oncology, Evelyn H. Lauder Breast Center, Memorial Sloan-Kettering Cancer Center, served as Acting Chair of the NCAB and presided during both the open and closed sessions. NCAB Members President’s Cancer Panel Dr. Samir Abu-Ghazaleh Dr. Harold Freeman (Chairperson) Dr. James O. Armitage Ms. Frances Visco Dr. Richard J. Boxer Mr. Stephen C. Duffy Alternate Ex Officio NCAB Members Dr. Ralph S. Freedman Dr. Steven K. Akiyama, NIEHS Dr. James H. French Dr. Michael A. Babich, USPSC Dr. Elmer E. Huerta Dr. T. G. Patel, VHA Dr. Frederick P. Li Dr. Peter Kirchner, DOE Dr. Susan M. Love Dr. Hugh W. McKinnon, EPA Dr. Sandra Millon-Underwood Dr.
    [Show full text]
  • Immunotherapy: Gene Therapy for Soft-Tissue Tumors
    RESEARCH HIGHLIGHTS Nature Reviews Clinical Oncology 8, 192 (2011); published online 1 March 2011; doi:10.1038/nrclinonc.2011.26 IMMUNOTHERAPY GENE THERAPY FOR SOFT-TISSUE TUMORS A T-cell receptor therapy directed against the NY-ESO-1 antigen causes tumor regression in patients with metastatic melanoma or synovial cell sarcoma, according to new research. “This study shows that cell transfer immunotherapy using T-cell receptor gene modified cells can be effective for the treatment of solid tumors other than melanoma,” explains senior investigator Steven Rosenberg. NY-ESO-1 is an antigen found in a number of cancers, including up to 50% of metastatic melanomas and 80% of synovial cell sarcomas. Rosenberg’s team investigated the effect of targeting this antigen in a small group of patients with melanoma or synovial cell sarcoma expressing NY-ESO-1 who had failed to respond to standard therapies. The technique, known as adoptive immunotherapy, involved treating patients with their own T cells, which were genetically modified to express T-cell receptors against NY-ESO-1. The treatment resulted in response rates of 45% in patients with melanoma and 67% in patients with synovial cell sarcoma. Tumor regression was observed in four of the six patients with synovial cell sarcoma and in five of the 11 patients with melanoma. One of the patients with synovial cell sarcoma had a partial response that lasted 18 months. Moreover, complete ongoing regression responses (for at least 20 months) were recorded in two patients with melanoma. No treatment-related toxic effects were observed. The findings indicate that T-cell receptor-based gene therapies directed against NY-ESO-1 offer an effective method for mediating tumor regression in metastatic melanoma and synovial cell sarcoma.
    [Show full text]
  • Tandem Minigene (TMG): String of Minigenes Encoding the Mutated AA Flanked by 12 AA on Each Side
    Presenter Disclosure Information Eric Tran The following relationships exist related to this presentation: No Relationships to Disclose 1 Identification of Antigens Targeted by Tumor Infiltrating Lymphocytes to Enhance Adoptive Immunotherapy SITC Workshop Nov. 5, 2015, National Harbor, MD Eric Tran, PhD Rosenberg Lab, Surgery Branch, NCI, NIH 2 Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) 3 Rosenberg and Restifo, Science , Apr 3 2015, 348 (6230): 62-68 Adoptive transfer of TIL can cure some patients with metastatic melanoma What antigens are recognized by TIL and are contributing to tumor regression? 4 T cells recognizing mutated antigens likely play a major role in the effectiveness of T-cell based therapies against melanoma Lu et al. Robbins et al. Van Rooij et al. Lu et al. Snyder et al. Van Allen et al. Can TIL therapy be effective in epithelial cancers such as gastrointestinal cancers with lower mutation burdens? 5 Conventional TIL therapy is largely ineffective against metastatic GI cancers Patient ID Tumor type Response PD : progressive disease SD : stable disease 3454 Colorectal PD PR : partial response 3596 Colon PD 3610 Rectal PD 3671 Colon PD 3674 Colorectal PD 3690 Colon PD 3717 Gastric PD 3737 Cholangio PD (13 mo SD ) Did T cells contribute to this response? 3788 GE junction PD If so, what do they recognize? Mutations? 3812 Cholangio PD 3894 Colon PD 3942 Rectal PD 3948 Esophageal PD 3970 Colon (Lynch) PD 3971 Colon PD 3978 Cholangio PD 6 Mutation-reactive T cells can be found in a patient with cholangiocarcinoma and appear capable of mediating tumor regression Rx2 Gated on CD4 (97%) Rx1 Gated on CD4 (55%) wt ERBB2IP mut ERBB2IP 0 0 3 93 wt ERBB2IP mut ERBB2IP 1 0 10 47 TNF 2 98 1 3 Vβ22 IL-2 43 56 38 5 Retreated with ~ 120 billion mutation- 1 0 10 50 ACT of > 10 billion mutation- reactive Vβ22+ Th1 cells (~ 95% of Rx2) reactive Th1 cells (~25% of Rx1) Cell Infusion TNF 43 56 37 3 200 Lung 0 0 8 47 Liver Total 150 γ Cell Infusion IFN- 44 56 40 6 100 Vβ22 Tumor burden Tumor Oct.
    [Show full text]
  • Corporate Presentation June 2017
    Corporate Presentation June 2017 © 2017, Lion Biotechnologies Forward-Looking Statements This presentation contains forward-looking statements reflecting management’s current beliefs and expectations. These forward looking statements can be identified with words such as “expects”, “plans”, “projects”, “potential”, “suggests”, “may”, or similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Forward-looking statements in this presentation include statements regarding (i) the success and timing of our product development activities and clinical trials, (ii) our ability, and the ability of our commercial partners, to manufacture, process and deliver our product candidates and to further improve on the manufacturing process, (iii) the size of the potential markets for our product candidates, (iv) our ability to develop next generation TIL and other more effective and efficient therapeutics, (v) our ability to maintain our collaborations and other relationships with third parties, including in particular with the National Cancer Institute/NIH, (vi) our ability to attract and retain key management and scientific personnel, (vii) our ability to obtain and maintain intellectual property protection for our product candidates, (viii) our ability to compete with other therapeutics that target the same indications as our product candidates, and (ix) our ability to achieve our manufacturing, clinical, regulatory, and other key milestones. For more detailed information about the risks and uncertainties that could cause actual results to differ materially from those implied by, or anticipated in, these forward-looking statements, please refer to the Risk Factors section of the Company’s Annual Report on Form 10- K and subsequent updates that may be contained in the Company’s Quarterly Reports on Form 10-Q and current reports on Form 8-K on file with the SEC.
    [Show full text]
  • The New Dawn of Immunotherapy
    THE BIOMEDICAL OPINION OPINION THE BIOMEDICAL 16 SCIENTIST One-to-one One-to-one SCIENTIST 17 Left. ACT using autologous lymphocytes targeting somatic mutations undergone one of the most rare events in medicine – a spontaneous regression.” Steven felt the explanation for this had STEVEN ROSENBERG THE NEW DAWN OF to be buried somewhere in the patient’s Chief of surgery at the immune system. “The body has hundreds National Cancer Institute of billions of lymphocytes,” he says, “and in Bethesda, Maryland Pre-treatment 14 Months IMMUNOTHERAPY somewhere in the body of the patient BA and MD degrees at there had to be lymphocytes that could Johns Hopkins University, Steven Rosenberg made headlines around the recognise what was different about the PhD in Biophysics at respond to all previous chemotherapy and unique mutations in a patient’s cancer globe for a breakthrough that could make cancer. This led us to identify the cells Harvard University hormonal treatment. can result in dramatic durable that were attacking the cancer and then Residency training in Steven describes his new technique as regressions,” says Steven. “This breast immunotherapy a frontline cancer treatment. use them to develop a cancer treatment.” surgery at the Peter Bent “a high-throughput method to identify cancer patient is now cancer-free based Steven and his colleagues subsequently Brigham Hospital in Boston, mutations present in a cancer that are on all available studies two-and-a-half isolated various types of immune cells Massachusetts recognised by the immune system. But years after treatment.” he idea of immunotherapy, century, it began to reawaken.
    [Show full text]