It is a critical moment for adoptive T cell therapies. With numerous clinical trials ongoing, particularly with Chimeric Antigen Receptors, all eyes are on therapy developers for better or for worse. Despite the attention, the end goal is the same – improved patient outcomes. Cambridge Healthtech Institute’s Fourth Annual Adoptive T Cell Therapy event will focus on the steps needed to deliver 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. Emphasis will also be placed on clinical case studies to further the understanding of T cell receptors and their biology. Additional focus will be given to manufacturing challenges and solutions for scale-up. Overall, this event will address clinical progress, case studies, and critical components to make adoptive T cell therapies viable.
Final Agenda
Recommended Short Courses*
SC3: Genomics in the Service of Cancer Immunotherapy - Detailed Agenda
SC11: Adoptive Therapy with CAR T Cells - Detailed Agenda
*Separate registration required
WEDNESDAY, MAY 3
7:30 am Registration and Morning Coffee
8:30 Chairperson’s Remarks
David Gilham, Ph.D., Vice President, Research & Development, Celyad S.A.
8:40 Fully Individualized Tumor Neoantigen-Based Vaccine Approaches to Cancer Therapy
Karin Jooss, Ph.D., CSO, Gritstone Oncology, Inc.
Genetic instability in tumors generates tumor-specific neo-antigens which have been identified as the targets of new T cells in patients responding to checkpoint inhibitor therapy. Predicting neo-antigens by sequencing routine clinical biopsy material and then incorporating them into therapeutic cancer vaccines is an attractive concept being developed by Gritstone Oncology. The complexities of neo-antigen prediction will be discussed, together with insights into how vaccine vectors are selected and designed.
9:10 Discovery and Development of Novel Immunogenic Tumor Neoantigens for the Treatment of Solid Tumors
Philip M. Arlen, M.D., President and CEO, Precision Biologics, Inc.
Immunogenic Neoantigens were derived from a membrane preparation of pooled allogeneic colorectal cancer from patients undergoing surgery. Membrane fractions were isolated and tested for immunogenicity and utilized in a clinical trial in patients with chemotherapy refractory metastatic colorectal cancer. A positive correlation was observed in patients who were able to mount and sustain IgG responses to vaccine. Antibodies were screened using this vaccine and tested for sensitivity, specificity, and anti-tumor function. Neoantigens were identified in colon cancer with these functional antibodies.
9:40 How Can We Utilize Neoantigens in Personalized Therapies for Patients with Tumors Having Low Mutation Profiles?
Markus Dangl, Ph.D., Senior Vice President Research and Pre-Clinical Development, Medigene AG
One important challenge in the use of neoantigens for personalized immunotherapies is to understand whether neoantigens are accessible as targets only for tumors of high mutational burden and/or limited to patients with pre-existing neoantigen-specific T cells. Medigene uses its immunotherapy platform technologies to investigate neoantigens as future targets for vaccines and adoptive T cell therapies exploring mutated targets in tumors with low mutational burden.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:55 New Targets in Hematologic Malignancies and Solid Tumors
J. Joseph Melenhorst, Ph.D., Director, Product Development & Correlative Sciences Laboratories (PDCS); Adjunct Associate Professor, Center for Cellular Immunotherapies, University of Pennsylvania
Revamping a patient’s own failed T cell repertoire with engineered tumor-targeting receptors has demonstrated efficacy with some chimeric antigen receptors (CAR). It has become clear that T cell-intrinsic and -extrinsic factors contribute to the clinical efficacy of this form of therapy. In my talk I will highlight several such mechanisms and novel ways in which we have turned our correlative sciences and product development studies in enhanced tumor targeting of CART cells
11:25 Overcoming CAR T Cell Checkpoint Blockade in Solid Tumors
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Prasad S. Adusumilli, M.D., F.A.C.S., Associate Attending and Deputy Chief, Thoracic Surgery, Memorial Sloan Kettering Cancer Center
CAR T-cell therapy for solid tumors is prone to the checkpoint blockade inhibition similar to innate tumor-infiltrating lymphocytes. Cell-intrinsic strategies to overcome this ‘Adaptive Resistance’ of infused CAR T cells can promote their functional persistence. Understanding solid tumor type-specific immune microenvironment can guide both cell-intrinsic and extrinsic strategies that can modulate the solid tumor microenvironment in addition to promoting CAR T-cell efficiency.
11:55 Enjoy Lunch on Your Own
1:55 Session Break
2:10 Chairperson’s Remarks
Prasad S. Adusumilli, M.D., F.A.C.S., Associate Attending and Deputy Chief, Thoracic Surgery, Memorial Sloan Kettering Cancer Center
2:15 Exploiting Natural Killer Receptors for CAR T Cell Therapy
David Gilham, Ph.D., Vice President, Research & Development, Celyad S.A.
The effector functions of Natural killer (NK) cells are controlled by a series of activating and inhibitory receptors that provides target discrimination for the NK cell. NKG2D is an activating NK receptor that binds to 8 known stress ligands. These ligands are highly expressed on tumor cells while expression on healthy tissue is minimal and provides a potential route to target a broad range of hematological and solid tumors. Pre-clinical studies of a NKG2D-CD3z CAR (NKR2) show potent anti-tumor activity and also suggest that T cells bearing the NKR2 receptor modulate the immune component of the tumor microenvironment and also potentially target tumor neo-vasculature. These data have supported the translation of NKR2 technology into the early stage clinical trial setting.
2:45 New T Cell Targets by Dissection of Successful Tumor-Infiltrating Lymphocyte Therapy for Melanoma
Andrew Sewell, Ph.D., Distinguished Research Professor and Wellcome Trust Senior Investigator, 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 Adoptive Cell Therapy for Cancer Using Tumour Infiltrating Lymphocytes
John S. Bridgeman, Ph.D., Director of Cell Therapy Research, Cellular Therapeutics, Ltd.
The prognosis for metastatic melanoma remains poor, and despite the success of novel immunotherapeutics, there exists an unmet need for new treatments. We have established a protocol to generate Tumour infiltrating lymphocytes (TIL) from surgically resected melanoma lesions. The results reported here support the success of melanoma TIL therapy seen in other centres worldwide and suggest that this is a viable means of treating a disease which has few effective options.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Problem-Solving Breakout Discussions
These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.
Combination Checkpoint Blockade Immunotherapies for Solid Tumors
Prasad S Adusumilli, M.D., F.A.C.S., Associate Attending and Deputy Chief, Thoracic Surgery, Memorial Sloan Kettering Cancer Center
- Best combination of agents for solid tumor therapy
- Best regimen of combination therapy for thoracic cancers
- Combination of CAR T-cell and checkpoint blockade agents
- Tumor immune markers following chemo and immunotherapy
Off-The-Shelf Immunotherapy: How Close Are We?
Bahram (Bob) Valamehr, Ph.D., MBA, Executive Director, Reprogramming Biology and Cancer Immunotherapy, Fate Therapeutics Inc.
- Patient centric versus product centric strategies
- Creating unlimited renewal source of cellular therapeutics
- Universal histocompatibility and elimination of alloreactivity
- Manufacturing uniform effector cells with augmented function
5:45 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 pm End of Day
THURSDAY, MAY 4
8:00 am Morning Coffee
8:30 Chairperson’s Remarks
Paul Beavis, Ph.D., Senior Postdoctoral Researcher, Cancer Immunotherapy, Peter MacCallum Cancer Centre
8:35 ImmunoMap: A Novel Bioinformatics Tool to Visualize and Analyze T-Cell Receptor Repertoire Sequence Data
Jonathan Schneck, M.D., Ph.D., Professor, Pathology Medicine and Oncology, Johns Hopkins University
We describe a novel method utilizing phylogenetic and sequencing analysis to visualize and quantify TCR repertoire diversity. To demonstrate the utility of the approach, we have applied it to understanding the shaping of the CD8 T Cell response to self (TRP2) and foreign (SIY) antigens in naïve and tumor-bearing B6 mice. We have developed and demonstrated a novel method to meaningfully parse and interpret TCR repertoire data and have applied it to yield a novel understanding of CD8 T Cell responses to different types of antigens.
9:05 Exploitation of T Cell Co-Stimulation for the Improvement of Adoptive T Cell Therapy
Abhishek Srivastava, Ph.D., Fellow, Surgery Branch, National Cancer Institute, NIH
Adoptive T cell therapy (ACT) involves the ex vivo stimulation and expansion of autologous tumor-infiltrating lymphocytes (TIL) and re-transfers into patients. However, current ACT strategy poses some limitations due to generation of sub-optimal TIL product for many patients which leads to poor survival, persistence and lack of effective anti-tumor efficacy of these cells after adoptive transfer. Therefore, utilization of a co-stimulatory signaling may play a critical role in restoring the survival, persistence and antitumor efficacy of these TILs in ACT.
9:35 First-in-Class Antibody Targeting Soluble NKG2D Ligand sMIC for Cancer Immunotherapy
Jennifer Wu, Ph.D., Professor, Hollings Cancer Center,Medical University of South Carolina; President and CSO, CanCure LLC
In response to oncogenic insult, human cells were induced to express a family of MHC I-chain related molecules A and B (MICA and MICB, generally termed MIC) on the surface which serve as the ligands for the activating immune receptor NKG2D expressed by all human NK, CD8 T, NKT, and subsets of γδ T cells. Theoretically, engagement of NKG2D by tumor cell surface MIC is deemed to signal and provoke the immune system to eliminate transformed cells. Clinically, almost all advanced tumors in cancer patients produce soluble MIC through proteolytic shedding mediated by metalloproteases, or by release in exosomes derived from the cell membrane. Tumor-derived sMIC is known to be highly immune suppressive and profoundly insults the immune system by downregulating receptor NKG2D expression on effector NK and T cells, driving the expansion of tumor-favoring myeloid suppression cells, skewing macrophages into alternatively activated phenotypes, and perturbing NK cell peripheral maintenance. High levels of serum sMIC significantly correlate with advanced diseases of many types of cancer. These observations clearly endorse sMIC to be a cancer immune therapeutic target. However, due to mice lack homologues to human MIC, this concept was not proven until our recent studies. Using a “humanized” MIC-transgenic spontaneous mouse model which recapitulates the NKG2D-mediated onco-immune dynamics of human cancer patients, we show that neutralizing circulating sMIC with a first-in-field non-blocking antibody B10 that does not block the interaction of MIC with NKG2D revamps endogenous innate and antigen-specific CD8 T cell responses. We show that therapy with the non-blocking sMIC-neutralizing antibody results in effectively debulking of primary tumor and elimination of metastasis, with no observed toxicity. Furthermore, we show that clearing sMIC with the first-in-class neutralizing antibody B10 also enhanced the efficacy of other cancer immunotherapeutic modalities, such as immune checkpoint blockade or adoptive cell-based therapy pre-clinically. Our study has launched a new avenue of cancer immunotherapy which can be readily translated into clinical trials.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
11:05 ACTR (Antibody Coupled T Cell Receptor): A Universal Approach to T Cell Therapy
Seth Ettenberg, Ph.D., CSO, Unum Therapeutics, Inc.
Fusing the ectodomain of CD16 to the co-stimulatory and signaling domains of 41BB and CD3z generates an Antibody Coupled T cell Receptor (ACTR). T cells expressing this receptor show powerful anti-tumor cytotoxicity when co-administered with an appropriate tumor-targeting antibody. Such cells have potential utility as a therapy to treat a wide range of cancer indications. We will describe efforts specifically targeting B-cell malignancies using a combination of ACTR T cells with Rituximab.
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, M.D., Ph.D., 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 cells can be expanded to 1010 within two weeks without feeder layer using FDA compliant medium. The safety of aNK as well as their activity against a broad range of cancers have been confirmed in several Phase I clinical trials in the U.S., Canada and Europe. The aNK cells can be administered in the outpatient setting and serve as a universal cell-based therapy without need for individualized patient matching. Moreover, 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 in the therapeutic setting.
12:05 pm Off-the-Shelf Cancer Immunotherapy: Engineered Pluripotent Cell-Derived Natural Killer Cells
Bahram (Bob) Valamehr, Ph.D., MBA, Vice President, Cancer Immunotherapy, Fate Therapeutics, Inc.
Harnessing the power of 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 “off-the-shelf” source of cellular therapeutics. By coupling the unique capacity of our pluripotent cell platform to efficiently facilitate multiple genomic modifications at the single cell level with our ability to accurately recapitulate the stages of hematopoiesis, we demonstrate a viable method for the derivation of efficacious engineered natural killer cells, genomically-engineered with augmented potency, persistence, targeting and safety mechanisms.
12:35 End of Adoptive T Cell Therapy