Adoptive Cell-Based Cancer Immunotherapy

Increased understanding of tumor immune biology as well as advances in genetic engineering, cell culture, and delivery have quickly positioned adoptive cell-based approaches as the next wave of successful immunotherapies, with remarkable efficacy already demonstrated in some trials. However, due to severe side effects of first-generation agents, developers are now working on improved T cell and a suite of NK cell therapies to join the ranks of already approved checkpoint antibodies.

Cambridge Healthtech Institute’s Inaugural Adoptive Cell-Based Cancer Immunotherapy symposium will convene an interdisciplinary collection of cancer researchers, drug developers, and technology providers to discuss current challenges, emerging approaches, and updates on T and NK cell-based cancer immunotherapies in the clinic.

Thursday, February 15

7:00 am Registration Open and Morning Coffee

ADVANCES IN NK CELL-BASED ADOPTIVE THERAPY

8:25 Chairperson’s Opening Remarks

Dean Anthony Lee, M.D., Ph.D., Professor, Pediatrics; Director, Cellular Therapy and Cancer Immunotherapy Program, Nationwide Children’s Hospital; James Comprehensive Cancer Center/Solove Research Institute, The Ohio State University

8:30 Novel Ways to Target and Activate NK Cells to Treat Cancer

Veronika Bachanova, M.D., Ph.D., Associate Professor, Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota

We have discovered a new subset of NK cells termed adaptive with properties of immunologic memory induced by cytomegalovirus, which we think has potent anti-tumor activity. These cells exhibit enhanced anti-tumor activity in vitro and in vivo. We have recently developed a method to expand these cells from CMV seropositive donors and are testing this product in clinical trials. Lastly, NK cells can be made antigen specific to target tumors through IL-15 tri-specific killer engagers (TriKEs) to enhance the activity of NK cells in the clinic.

9:00 Update: aNK and haNK for Cancer Treatment

David Pyrce, Ph.D., Senior Vice President, Innovation & Chief Commercial Officer, NantKwest, Inc.

I will provide an update on clinical trial activities with aNK haNK cells expressing the high affinity Fc-Receptor for combination therapy with mAbs taNK cells engineered to express CARs for neo-epitopes. I will also discuss augmenting NK activity with IL-15 super-agonist Altor 803, as well as optimizing NK target activity through CRISPR-based gene manipulation.

9:30 Pluripotent Cell Derived T and NK Cells: Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy

Dean Anthony Lee, M.D., Ph.D., Professor, Pediatrics; Director, Cellular Therapy and Cancer Immunotherapy Program, Nationwide Children’s Hospital; James Comprehensive Cancer Center/Solove Research Institute, The Ohio State University

(From Fate Therapeutics) We’ve developed a unique and effective strategy to create a renewable source of genetically engineered “off-the-shelf” T and NK cells with augmented function. Through targeted transgene integration, we produced a clonal pluripotent cell master cell line to continuously produce T and NK cells engineered to uniformly express selected modalities. Preclinical data highlight the therapeutic value of this approach to generate ideal T and NK cell-based immunotherapeutic products with augmented persistence, anti-tumor capacity, manufacturing reliability and preclinical efficacy.

10:00 Late Breaking Presentation    

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

NK CELL IMMUNO-ONCOLOGY AND CLINICAL STUDIES

11:15 Utilizing Immunostimulatory Cytokines to Unleash Natural Killer Cell Anti-Tumor Responses

Amanda Cashen, M.D., Associate Professor, Medicine, Division of Leukemia and Stem Cell Transplantation, Washington University School of Medicine

Memory-like NK cells exhibit enhanced functional response to leukemia and other malignancies in vitro and in vivo, and recently have shown promise in a first-in-human early phase clinical study for patients with acute myeloid leukemia. IL-15 receptor super agonist complexes provide in vivo endogenous IL-15 receptor trans-presentation, and may be harnessed to support the expansion and functional capacity of NK cell in cancer patients. Thus, cytokine function-enabled NK cells represent an innovative translational immunotherapy approach for cancer patients.

11:45 Adoptive Immunotherapy with Expanded NK Cells - The Impact of STAT3 Signaling and Crosstalk with Adaptive Immunity

Dean Anthony Lee, M.D., Ph.D., Professor, Pediatrics; Director, Cellular Therapy and Cancer Immunotherapy Program, Nationwide Children’s Hospital; James Comprehensive Cancer Center/Solove Research Institute, The Ohio State University

We developed a system for ex vivo NK cell expansion based on genetically modified feeder cells expressing IL-21, which through STAT3 signaling induces robust activation and proliferation of NK cells from normal donors, patients, cord blood, and embryonic/pluripotent stem cells. We established the GMP infrastructure to manufacture clinical-grade NK cells using this approach, and infused expanded NK cells into patients as monotherapy, in single or repeated infusions, or in combination with chemotherapy or stem cell transplantation.

12:15 pm Enjoy Lunch on Your Own

CAR-T CELLS FOR SOLID TUMORS

1:55 Chairperson’s Remarks

Joseph A. Fraietta, Ph.D., Associate Director, Product Development, Center for Advanced Cellular Therapeutics, University of Pennsylvania

2:00 New Targets in Hematologic Malignancies and Solid Tumors

Joseph A. Fraietta, Ph.D., Associate Director, Product Development, Center for Advanced Cellular Therapeutics, 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 CAR-T cells.

2:30 Overcoming CAR-T Cell Checkpoint Blockade in Solid Tumors

Prasad S. Adusumilli, M.D., FACS, 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.

3:00 GOLDCARs – T Cell Activation Triggered Mechanism for Delivery of Tumor Microenvironment Remodeling Payloads to Enhance T Cell Responses against Solid Tumors

Ben Wang, Ph.D., CEO, Chimera Bioengineering

3:30 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

4:15 Talk Title to be Announced

Janet R. Rea, MSPH, RAC, Senior Vice President, Regulatory, Quality and Clinical Affairs, Atossa Genetics, Inc.

4:45 Addressing Safety and Efficacy to Harness T Cell Therapies’ Full Potential

David M. Spencer, Ph.D., CSO, Bellicum Pharmaceuticals

Despite great fanfare, adoptive cell therapies for solid tumors are still limited by efficacy and safety challenges. Non-homogeneous antigen expression, low-level expression on healthy tissue, and unpredictable persistence of therapeutic cells all contribute to the high variability in performance by these “living drugs”. Using chemically induced dimerization (CID) that taps into fundamental properties of cell biology, we have developed orthogonal switches that permit regulation of T cell activity and persistence alongside survival control to reign in toxicity. Independent regulation of co-stimulation and apoptosis in the same cell is now possible using a scalable, clinically compatible process.

5:15 FEATURED PRESENTATION: Tricked-Out Cars, the Next Generation of CAR-T Cells

Benjamin Boyerinas, Ph.D., Senior Scientist, bluebird bio

Genetically-engineered CAR-T cells are designed to supplement a patient’s immune system and can be further engineered to survive and overcome immune evasion mechanisms employed by tumors. We found that addition of a PI3-kinase inhibitor during manufacturing enriched for memory-like CAR-T cells without complicated cell sorting procedures. These methodologies, combined with synthetic biology and gene editing, can be considered for the further development of CAR-T cell technology.

5:45 Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Day

Friday, February 16

8:00 am Registration Open and Morning Coffee

NEXT-GENERATION CAR-T DISCOVERY AND DEVELOPMENT PLATFORMS

8:25 Chairperson’s Remarks

Harjeet Singh, Ph.D., Research Scientist, Pediatrics, University of Texas MD Anderson Cancer Center

8:30 FEATURED PRESENTATION: Sleeping Beauty: An Update on the Non-Viral Transduction Platform for CAR Therapies

Harjeet Singh, Ph.D., Research Scientist, Pediatrics, University of Texas MD Anderson Cancer Center

During this presentation, I will discuss viral versus non-viral transduction for CAR-T cells, evaluate clinical trial results at MD Anderson Cancer Center using CARs transduced with the non-viral Sleeping Beauty platform, and discuss the future plans for Sleeping Beauty CARs.

9:00 Multivalent Adoptive Cell Therapy Using Novel XPRESIDENT®-Derived Targets

Steffen Walter, Ph.D., CSO, Immatics US, Inc.

Tumor evasion due to tumor heterogeneity or antigen loss is a major limitation for the successful treatment of solid tumors using adoptive T cell therapy. Multivalent approaches using multiple relevant targets in parallel should be a solution to this problem, however they have been conducted in only a very limited way due to lack of safe and validated targets. The XPRESIDENT® platform allows access to a novel target space using a combination of ultra-sensitive quantitative mass spectrometry, transcriptomics, immunology and bioinformatics based on the immunopeptidome of human normal and tumor tissues. We present data from one clinical-stage platform (ACTolog®) using up to four validated targets per patient, and provide an update to a complementary, genetically engineered approach, ACTengine®.

9:30 Targeting Glioblastoma with Allogeneic EGFRvIII-Specific Chimeric Antigen Receptor T Cells

Oi Kwan Wong, Ph.D., Senior Principal Scientist, Tumor Biology, Pfizer, Inc.

EGFRvIII is a tumor specific mutant of EGFR found in 25-30% of glioblastoma multiforme but not expressed in healthy tissues. Thus, it is an attractive target for CAR-T cell therapy. We engineered EGFRvIII-specific CAR-T cells that effectively eliminated both cell line derived and patient derived xenograft models of GBM expressing the mutant receptors. Moreover, intravenously delivered EGFRvIII CAR-T cells were able to traffic to the brain and eliminated tumors in an intracranial model of GBM. Our goal is to develop an effective allogeneic CAR-T to treat patients with EGFRvIII positive GBM.

Xyphos 10:00 ConvertibleCAR-T Cells Provide Dose Control of Activity with Sequential and Multiplex Targeting

Kaman Kim, Ph.D., Senior Scientist, Project Leader, Xyphos Inc.

ConvertibleCAR-T cells possess an inert NKG2D receptor that binds exclusively to an orthogonal human ligand fused to a complete antibody (MicAbody) to target a specific tumor antigen. Studies in NSG mice have demonstrated MicAbody dose-dependent killing of tumors. Targeting can be switched or multiplexed without modifying the convertibleCAR-T cell, and hence, one autologous convertibleCAR-cell suffices for all targets in the donor patient or one allogeneic convertibleCAR-cell will suffice for all patients, all targets.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

NEXT-GENERATION CAR-T DISCOVERY AND DEVELOPMENT PLATFORMS (CONT.)

11:15 TRuC™-T Cells: A Novel Kind of Engineered T Cells for Solid Tumors Exploiting the Signaling Power of the Complete T Cell Receptor

Robert Hofmeister, Ph.D., CSO, TCR2 Therapeutics, Inc.

Here, we present a novel, non-MHC restricted therapeutic platform for engineering T cells (TRuC™) that is based on the direct fusion of antigen binding domains to subunits of the T cell receptor (TCR) complex. Unlike CARs, which do not integrate into the TCR, TRuC™ variants become part of the TCR and power T cells through the complex signaling cascade of the TCR. TRuC™-T cells potently killed tumor cells in vitro and thereby released less cytokines than respective CAR-T cells.

11:45 4-1BB-Based Adoptive T Cell Therapy

Myung Kim, Ph.D., Vice President and COO, Eutilex Institute of Biomedical Research, Eutilex, Co., Ltd.

We have developed a practical protocol to produce antigen-specific CD8+ T cells from peripheral blood mononuclear cells (PBMCs), based on a unique property of 4-1BB (CD137) — the selective expression on Ag-engaged T cells. We have proven the feasibility of this procedure by isolating and expanding shared Ag (hTERT, WT1, NY-ESO1, and EBV)-specific CD8+ T cells, and applied to produce Neo-Ag-specific CD4+ and CD8+ T cells. Our protocol can readily be translated into standard cGMP and is being used to produce EBV-, hTERT-, and WT-1-specific CD8+ T cells for Phase I clinical trials.

12:15 pm Close of Symposium


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