These are very exciting times for adoptive cell therapies. The FDA has approved the first two CAR Therapies for sale in the US, and momentum is already building behind the next generation of CARs, TCRs and TILs offering superior targeting and safety
profiles. Cambridge Healthtech Institute’s Fifth Annual CAR Ts, TCRs and TILs event will focus on the critical developments, clinical progress and latest research driving the delivery of adoptive cell therapies to the patient. Clinical progress
with Chimeric Antigen Receptors (CAR), T Cell Receptors (TCR), and Tumor Infiltrating Lymphocytes (TIL) will be addressed in depth and new strategies for target discovery will be reviewed.
Final Agenda
SC9: CAR T Cell Therapy for Solid Tumors
Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School
Moonsoo M. Jin, PhD, Associate Professor, Molecular Imaging Innovations Institute, Radiology, Weill Cornell Medical College
Tara Arvedson, PhD, Director, Oncology Research, Amgen
*Separate registration required.
WEDNESDAY, MAY 2
7:30 am Registration(Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Remarks
Mark Bonyhadi, PhD, Head, Research, Juno Therapeutics
8:40 KEYNOTE: Future Challenges in Adoptive T-Cell Therapy
Michel Sadelain, PhD, Director, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center
9:10 Development of Yescarta (Axicabtagene Ciloleucel), a First in Class CAR T Cell Product for Diffuse Large B Cell Lymphoma: A Translational Perspective
Adrian Bot, MD, PhD., Vice President, Translational Sciences, Kite, a Gilead Company
Yescarta (Axicabtagene Ciloleucel) is an anti-CD19 CAR T cell therapy that received recently approval for treatment of relapsing or refractory DLBCL. Yescarta met its primary endpoint with 82% objective response rate, 54% complete response and 44%
ongoing response at 6 months. This presentation will describe key elements of the translational program, correlates of toxicities and durable objective response, product characteristics, patient conditioning, and importance of tumor microenvironment.
9:40 Development of an Anti-BCMA CAR T Cell Therapy That Delivers Durable Clinical Responses in Relapsed/Refractory Multiple Myeloma
Molly Perkins, DPhil, Associate Director, Immunotherapy, bluebird bio
Our first anti-BCMA CAR T cell product candidate, bb2121, has demonstrated encouraging safety and efficacy in a Phase I trial for relapsed/refractory multiple myeloma. bb21217 is a second anti-BCMA clinical product candidate which is manufactured
in the presence of a PI3k inhibitor, leading to a CAR T cell product enriched for potent, long-lived memory T cells. The preclinical and clinical data on bb2121 and bb21217 will be discussed, highlighting the key scientific lessons learned.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
10:55 CAR-Specific Activation and Kinetics of a BCMA-Directed CAR
Collin Hauskins, Research Scientist, Protein Sciences, Juno Therapeutics
Mark Bonyhadi, PhD, Head, Research, Juno Therapeutics
Reagents that specifically bind the CAR on genetically engineered cells may be used to detect and quantitate surface CAR expression, and can also be used to stimulate the CAR T cell directly through their engineered receptor. We describe
the production of reagents that bind to CD19- and BCMA-directed CAR T cells. These reagents are capable of specifically activating and expanding CAR T cells, allowing us to interrogate the biology of CAR signaling. These reagents could
have further applications in the manufacturing of CAR T cells.
11:25 Dual-Switch CAR T Cells: Orthogonal Molecular Switches to Control Activation and Elimination of Cancer-Targeted CAR T Cells
J. Henri Bayle, PhD, Director of Molecular Biology, Research and Development, Bellicum Pharmaceuticals
Chimeric Antigen Receptor (CAR) therapies are effective against disseminated cancers but often lack control over T cell efficacy and persistence against off-tumor reactivity and excessive cytokine release. Two platforms were engineered
to separate tumor antigen-targeted first-generation CARs from an inducible costimulatory component, iMyD88/CD40, and a pro-apoptotic safety switch based on Caspase-9. These switches are orthogonally controlled by high-affinity, cell-permeable
ligands, rimiducid and rapamycin analogs that direct targeted protein oligomerization.
11:55 Carjacking CAR19 T Cells for Redirected Killing
Paul Rennert, PhD, President & CSO, Aleta Biotherapeutics Inc
CAR19 cellular therapeutics benefit from interaction with bona fide antigen-presenting B cells (both normal and malignant). The integration of fusion protein modules into CAR19 lentiviral constructs endows CACR19s with novel antigen recognition
properties. These highly potent CARjacked CAR19s recognize both CD19 (directly) and novel antigens (redirected) enabling efficient cytotoxicity against diverse tumor types. The utility of this platform technology will be demonstrated
for hematologic malignancies and solid tumors.
12:25
pm Convertible CAR-T Cells Provide Dose Control of Activity and Targeting Flexibility
Kaman Kim, PhD, Vice President, Research, Xyphos
Current CAR cellular therapies have a number of limitations that impact their efficacy and perseverance in clinical settings including single antigenic targeting, utilization of non-human components, and lack of dose control. The Xyphos
convertibleCARTM platform functions as a flexible and controllable system to address these limitations and maximize therapeutic versatility.
12:55 Enjoy Lunch on Your Own
1:55 Session Break
2:10 Chairperson’s Remarks
Adrian Bot, MD, PhD., Vice President, Translational Sciences, Kite, a Gilead Company
2:15 Optimized Manufacturing SPEAR TCR T-Cell Therapy for Solid Tumors
Mark Dudley, PhD, Senior Vice President, Bioprocessing & Development CMC, Technical Operations, Adaptimmune
Specific peptide enhanced antigen receptor (SPEAR) T-cells that are genetically re-targeted to tumors can be part of an effective therapy regimen for some refractory solid cancers. SPEAR T-cells targeting NY-ESO show promise in synovial
sarcoma and other indications. MAGE-A10, MAGE-A4, and AFP are currently being evaluated in early phase clinical trials. Opportunities and challenges for optimizing a single cGMP platform to manufacturing products for multiple indications
will be discussed.
2:45 Learning What Works from Successful Tumor Infiltrating Lymphocyte Therapy
Andrew Sewell, PhD, Professor, Division of Infection and Immunity, Cardiff University School of Medicine
Over 20% of melanoma patients that have been refractory to other treatments undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating lymphocytes (TILs). Dissection of these extraordinary successes by examining
the dominant tumor-reactive T-cell clonotypes in the TIL infusion product and patient blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and non-HLA restricted targets that are expressed by many
other tumour types.
3:15 Novel Phosphopeptide-Specific TCRs for Cancer Cell Therapy
Arthur A. Hurwitz, PhD, Vice President, Head of Preclinical Research, AgenTus Therapeutics
Agenus has developed two enabling platform technologies to identify PTT-specific T cell receptors (TCRs): 1) a primary T cell expansion protocol wherein PTT-specific cognate TCRαβ pairs are identified by functional screening
and/or NGS-based sequencing; and 2) a TCR display platform comprising the generation of TCR α and β chain libraries from healthy donor PBMCs, followed by several rounds of TCR enrichment for PTT-specific binding. We have
used these platforms to derive fully-human TCRs from central memory T cells of healthy individuals. Importantly, we demonstrate that these TCRs derived from the central memory compartment are highly potent at killing tumor cell lines
displaying their cognate PTTs. Phosphopeptide recognition was sequence-specific and depended on the phosphoseryl moiety. The discovery of phosphopeptide-specific TCRs derived from the memory compartment of healthy donors implies prior
immunological response to these phosphopeptides and also reveals TCRs that are expected to possess a preferential safety profile. Thus, these and other phosphopeptide-specific TCRs constitute prime candidates for clinical development.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:45 Problem-Solving Breakout Discussions (Commonwealth Hall)
Present and Future Of Genetically Engineered T Cells In Oncology
Adrian Bot, MD, PhD., Vice President, Translational Sciences, Kite, a Gilead Company
- Innovative receptor designs
- Desired features of T cells: potency and controllability
- Manufacturing optimizations to scale out, diminish cost, and fully utilize this platform technology
- Beyond blood cancers and beyond cancer: what is next ?
Commercial Manufacturing of Gene-Modified Cell Therapies: The Challenges Ahead
Michael D. Jacobson, PhD., Managing Partner, Cambridge Biostrategy Associates
- What are the most important problems that need to be solved over the next 3-5 years for this industry to thrive?
- What key innovations would you like to see that you believe would be transformative?
- How low do COGS need to go, and how (and when) will we get there?
- How automated and integrated will cell therapy manufacturing become over the next 5-10 years? What parts of the workflow are most ripe for integration, and which are not?
Off-the-Shelf Cancer Immunotherapy
Bob Valamehr, PhD, Vice President, Cancer Immunotherapy, Fate Therapeutics
- Ability to create a homogenous effector cell population from a clonal population of genetically edited starting population
- Generation of a renewable source for large scale manufacturing of cellular therapeutics
- Strategies to create a universal cellular product to overcome the histocompatibility barrier of a diverse patient population
5:45 Networking Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:00 End of Day
THURSDAY, MAY 3
8:00 am Registration(Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Remarks
Bob Valamehr, PhD, Vice President, Cancer Immunotherapy, Fate Therapeutics
8:35 Adaptive NK Cells and Off-the-Shelf NK Cells to Treat Cancer
Jeffrey S. Miller, MD, Professor of Medicine, Deputy Director, Masonic Cancer Center, Division of
Hematology, Oncology and Transplantation, University of Minnesota University of Minnesota
Cytomegalovirus exposure is uniquely associated with the expansion of natural killer (NK) cells that express NKG2C and the maturation marker CD57. Adaptive NK cells are epigenetically primed for enhanced anti-tumor activity alone
and in combination with CD16 signaling. Clinically, adaptive NK cells should result in superior anti-cancer effectors from CMV+ donors or from off the shelf iPS derived NK cells genetically modified to mimic functional attributes
of adaptive NK cells.
9:05 Combining Innate and Adaptive Immunity: NK Receptors for CAR T Cell Therapy
Peggy Sotiropoulou, PhD, Manager, Research and Development, Celyad
Natural Killer cells possess innate capacity to target ‘abnormal’ cells through the recognition of a range of target ligands, many of which are present on tumor cells. Engineering NK receptors into a CAR format and
expressing in T cells takes advantage of both NK specificity and T cell effector functionality. This approach will be discussed in the context in the pre-clinical setting and discussion of on-going clinical trials testing this
approach.
9:35 Combinatorial IL13Rα2 Chimeric Antigen Receptor-T Cells Plus Checkpoint Blockade to Treat Solid Tumors in Murine and Canine Models
Yibo Yin, MD, Postdoc Fellow, DEPT of Neurosurgery, Perelman School of Medicine, University of Pennsylvania
We made two fully humanized IL13Ra2 targeting CAR-T cells for the treatment of human solid tumors. We also made canine IL13Ra2 targeting CAR-T cells binding the same epitope as human IL13Ra2 CAR for the treatment of canine solid
tumor patients and translational research. The combination therapy of IL13Ra2 CAR-T cells were studies with systematically or locally delivered checkpoint blockades.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
11:05 Pluripotent Cell Derived T and NK Cells: Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy
Bob Valamehr, PhD, Vice President, Cancer Immunotherapy, Fate Therapeutics
Pluripotent cell technology represents a powerful approach to make cell-based immunotherapies available to a wide range of patients through the generation of a consistent and renewable “off-the-shelf” source of cellular
therapeutics. I will discuss our progress towards developing unique and effective strategies to create a renewable source of genetically engineered “off-the-shelf” T and NK cells with augmented function. Updates
on IND filings and FIH progress will also be given.
11:35 Continuously Growing NK Cell Line as a Source for an Off-the-Shelf, Engineered NK Cell Therapeutic in Cancer and Infections
Hans Klingemann, MD, PhD, Vice President, Research & Development, NantKwest, Inc.
NantKwest has developed the NK cell line NK-92 into an “off the shelf” activated NK (aNK) cell therapeutic. The safety of aNK as well as their activity against a broad range of cancers have been confirmed in several
Phase I clinical trials. The aNK cells can be administered in the outpatient setting and serve as a universal cell-based therapy without need for individualized patient matching. The aNK cell platform has been bioengineered
to incorporate a high-affinity antibody binding Fc-receptor (haNK). Both aNK and haNK cells can be equipped with chimeric antigen receptors (CARs) (called taNK) to further optimize targeting and potency.
12:05 pm Progress in Tumor Infiltrating Lymphocytes in Treatment of Solid Tumors
Maria Fardis, PhD, CEO, Iovance
Iovance Biotherapeutics is focused on the development and commercialization of novel cancer immunotherapies based on tumor infiltrating lymphocytes (TIL). In Phase 2 clinical trials conducted at the NCI, 56% and 24% of patients
treated with this technology were reported by NCI to have achieved objective and complete response criteria, respectively. Our lead product candidate is an autologous, ready-to-infuse cell therapy, that has demonstrated distinctive
efficacy in the treatment of metastatic melanoma.
12:35 End of CAR Ts, TCRs and TILs