Greater understanding of T cell biology as well as promising patient outcomes have led to immunotherapies accelerating at an unprecedented pace. However, with the end goal being the same – improved patient outcomes – there is still work to be done. Cambridge Healthtech Institute’s 5^th Annual Adoptive T Cell Therapy 1: Discovery conference focuses on the steps needed to select, engineer, enhance, and deliver promising T cell therapies to the patient.

Final Agenda

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Speaker Biographies | Participating Companies | Emerging Company Showcase Presenters

TUESDAY, AUGUST 28

12:00 pm Registration

NEW TECHNIQUES IN T CELL ENGINEERING

1:25 Chairperson’s Opening Remarks

David M. Spencer, PhD, CTO, R&D, Bellicum Pharmaceuticals

1:30 Mechanical Modality to Reengineer and Edit Cells for Enabling Cell/Gene Therapies

Steven Banerjee, CEO, Mekonos, Inc.

We are developing a universal scalable cargo delivery platform using silicon semiconductor technology to transport any type of molecular payload to any cell type outside the body to genetically reprogram single cells on a massively parallel scale before transplanting them into the patient. The overall portable system when fully developed will contain an assembly line of chips with independently controlled nanoneedles driven by a control and automation infrastructure.

2:00 Soluporation Vector-Free Intracellular Delivery Method for Engineering Immune Cells

Shirley O’Dea, PhD, CSO, Avectas Ltd.

Non-viral methods of intracellular delivery of various cargo types are attractive candidates as next-generation delivery modalities because of potential benefits for safety, cost, and production. We have developed a novel non-viral method termed ‘soluporation’ that achieves efficient intracellular delivery through reversible permeabilization of the cell membrane. Here we describe successful engineering of primary human T cells by soluporation and demonstrate high levels of cell viability and functionality in the modified cells.

2:30 Orthogonal 2D Control Of ACT: Not All Switches Are Created Equal

David M. Spencer, PhD, CTO, R&D, Bellicum Pharmaceuticals

Adoptive cell therapies for solid tumors are still limited by numerous efficacy and safety challenges. Non-homogeneous antigen expression, low-level expression on healthy tissue, unpredictable persistence of therapeutic cells and numerous immunosuppressive factors all contribute to inconsistency in these “living drugs”. Using chemically induced dimerization (CID) technology, we developed orthogonal on/off switches, permitting simultaneous regulation of T cell activity, persistence and survival in vivo, leading to robust anti-tumor efficacy in vivo.

3:00 Sponsored Presentation (Opportunity Available)

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 PLENARY KEYNOTE SESSION

4:20 CAR-T Therapy for B Cell Malignancies

Jennifer Brogdon, PhD, Director, Exploratory Immuno-Oncology, Novartis

4:55 Walking on the Moon: Reflections on the Work of the Cancer Moonshot and the Future of the Biden Cancer Initiative

Catharine Young, PhD, Senior Director, Science Policy, Biden Cancer Initiative

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

5:30 Dinner Short Course Registration*

*Separate registration required.

6:30 End of Day

6:30-9:00 pm Dinner Short Course

SC1: Bioinformatics for Immuno-Oncology and Translational Research

6:30-9:00 pm Dinner Short Course

SC2: Next-Generation Immunotherapies: Part 1

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WEDNESDAY, AUGUST 29

7:30 am Morning Coffee

INNOVATIONS IN IMMUNOTHERAPIES

8:25 Chairperson’s Remarks

Shulin Li, PhD, Professor, Director, Pediatric Laboratory Research Programs, W.T. and Louise Jarrett Moran Distinguished Chair, Pediatric Oncology, Pediatric Research, MD Anderson Cancer

8:30 Detection and Therapeutic Application of HLA/Peptide Complexes

William Hildebrand, PhD, ABHI Diplomate, Chief Scientist, Pure MHC

T cells utilize HLA/peptide complexes to distinguish infected and cancerous cells from healthy cells. We first describe how proteomics can be used to identify HLA/peptide complexes distinct to tumor and infected cells. Next, we illustrate how complementary immunologic methods can be used to validate that select HLA/peptide complexes are indeed distinct to unhealthy cells. Finally, we demonstrate that HLA/peptide complexes successfully transition into immune therapies for infectious disease and cancer.

9:00 Novel Immunomodulatory Strategy of Targeting Glyco-Immune Checkpoints with EAGLE Technology

Li Peng, PhD, Vice President, Biotherapeutics Discovery, Palleon Pharmaceuticals

Tumors exploit a previously unappreciated axis of immunosuppression through alteration of their cell surface glycans, which impairs multiple types of innate and adaptive immune cells critical to the anti-tumor response. Immune cells are “tricked” by these tumor-specific glycan patterns, such as hypersialylation, which makes them unable to detect and destroy cancer cells. This immunosuppression axis appears to be present in the majority of cancer types. We developed an EAGLE (Enzyme-Antibody Glyco-Ligand Editing) technology to modify tumor-specific glycans. Systematic delivery of a multi-functional antibody-like EAGLE molecule decreased sialic acid levels and increased T cell infiltration and activation in tumors. EAGLE treatment cured most mice of established tumors and led to resistance to rechallenge in syngeneic models. In summary, we revealed a novel immunomodulatory strategy by targeting glyco-immune checkpoints for the treatment of various cancers.

9:30 Fully Automated Isolation of Cell Subsets Straightfrom® Blood Products: Whole Blood, Buffy Coat, Leukopak, LRSC

Lotta Raety, Product Manager, Cell Separation, Marketing, Miltenyi Biotec

Isolating leukocytes from blood products is a key step in many cell-based assays. The MultiMACS X cell separator together with the StraightFrom MicroBeads offers fully automated isolation of cell subsets directly from your starting material. Eliminating density gradient centrifugation, the combination provides efficient and standardized cell separation from blood products.

9:45 Sponsored Presentation (Opportunity Available)

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 A Unique Approach to Adoptive Cell Therapy: Harnessing Super Immunity

Matthew E. Colpoys, Jr., Co-Founder & CEO, Tactiva Therapeutics

Tactiva’s DEACT approach combines “super immune cells” with epigenetic up-regulation of the target antigen to deliver powerful anti-tumor activity and overcome the T cell exhaustion associated with single TCR therapy. The platform includes a unique CD8 construct that includes both an NY-ESO-1 targeting TCR and dominant negative TGF beta, along with HSC cells engineered to differentiate into mature CD4 T cells with a “tumor recognizing” TCR targeting NY-ESO-1. Both TCRs are unique natural clones.

11:15 Simple Therapeutic Approach for Overcoming Solid Tumor Heterogeneity and Boosting T Cell Infiltration/Function

Shulin Li, PhD, Professor, Director, Pediatric Laboratory Research Programs, W.T. and Louise Jarrett Moran Distinguished Chair, Pediatric Oncology, Pediatric Research, MD Anderson Cancer

While great progress has been made in T cell therapy for cancer, several major gaps still block the success of CAR T cell or TIL therapy against solid tumors. The major barriers to CAR T cell efficacy in solid tumors include heterogeneity (lack of a unique and universal target), poor T cell penetration/accumulation in tumors, and an inert tumor microenvironment. Even successful CAR T therapy for liquid tumors faces a major challenge, cytokine release syndrome (CRS), in about 50% of patients. Therefore, a T cell therapy with the capacity to overcome these challenges is urgently needed. TIL therapy is limited to only some melanoma patients because of failed T cell expansion in vitro, lost T cell activity, and poor penetration in vivo in large percentages of patients. The presenter provides a simple strategy to address these issues.

11:45 Characterizing the Effects of Sex and Estrogen Signaling on the Function of Antigen-Specific T Cells For Immunotherapy

Flor C. Navarro, Research Scientist, Stephanie K. Watkins Laboratory, Biochemistry and Molecular Biology, Loyola University Chicago

I investigate sex-specific differences mediated by sex hormone signaling, specifically estrogen, on the antigen-specific T cell function and anti-tumor immune response. I use hepatocellular (HCC) carcinoma antigen-specific T cells generated from HCC tumor infiltrating lymphocytes. Using these T cells, I studied the effects of sex and estrogen receptor signaling on T cell function including cytokine production and polyfunctionality, as well as the T cell anti-tumor immune response in a HCC mouse model.

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Session Break

OFF-THE-SHELF IMMUNOTHERAPIES

1:40 Chairperson’s Remarks

Bob Valamehr, PhD, MBA, Vice President, Cancer Immunotherapy, Fate Therapeutics

1:45 Synthetic Biology for Cellular Cancer Immunotherapy

Wilson Wong, PhD, Assistant Professor, Biomedical Engineering, Boston University

I present a split, universal, and programmable (SUPRA) CAR system that simultaneously encompasses multiple critical “upgrades”, such as the ability to switch targets without re-engineering the T cells, finely tune T cell activation strength, and sense and logically respond to multiple antigens. Furthermore, we extend the orthogonal SUPRA CAR system to regulate different T cell subsets independently, demonstrating a dually inducible CAR system.

2:15 Synthetic Cells as Platforms for Programmed Drug Manufacturing Inside Tumors

Avi Schroeder, PhD, Assistant Professor, Chemical Engineering, Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Technion – Israel Institute of Technology

Synthetic cells are artificial systems capable of replacing malfunctioning cells in the body. The talk discusses principles for rationale design of remotely activated synthetic cells and their capacity to treat disease. Specifically, synthetic cells were evaluated as autonomous systems for producing therapeutic proteins inside tumors. Synthetic cells can exceed certain natural functions, such as producing biologics at large amounts or producing therapeutic proteins that are toxic to living cells. The technological versatility of synthetic opens a new door for tailoring personalized medicines to each patient.

2:45 Adaptive Cancer Immunotherapies

Timothy K. Lu, MD, PhD, Associate Professor, Synthetic Biology Group, Research Laboratory of Electronics, Electrical Engineering and Computer Science, Biological Engineering, Massachusetts Institute of Technology

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Genome Editing for “Off-the-Shelf” Allogeneic CAR T Cell Products

Julianne Smith, PhD, Vice President, Translational Sciences, Cellectis

Chimeric antigen receptor (CAR)-redirected T cells have given rise to long-term durable remissions and remarkable objective response rates in patients with refractory leukemia, raising hopes that a wider application of CAR technology may lead to a new paradigm in cancer treatment. A limitation of the current autologous approach is that CAR T cells must be manufactured on a "per patient basis". Cellectis has developed a platform for generating chimeric antigen receptor (CAR)-redirected T cells from third-party healthy donors using transcription activator-like effector nucleases (TALEN®). Nuclease mediated inactivation of the TCR alpha abrogates the potential for T cells bearing alloreactive TCRs to mediate Graft versus Host Disease (GvHD). Additional gene inactivation events can be incorporated, permitting resistance to lymphodepleting or chemotherapeutic agents, resistance to tumor inhibition or suppression of cross T cell reactions. Such allogeneic “off-the-shelf” CAR T cell products will permit a wider application of CAR technology and potentially lead to a new paradigm in cancer treatment.

4:30 Engineered Natural Killer Cells Expressing Enhanced Fc Receptors for Cancer Cell Killing

Bruce Walcheck, PhD, Professor, Immunology, University of Minnesota

A key anti-tumor function of natural killer (NK) cells is antibody-dependent cell-mediated cell cytotoxicity (ADCC) induced upon their engagement of tumor-bound antibodies. Many clinically successful tumor-targeting therapeutic monoclonal antibodies (mAbs) utilize ADCC as a mechanism of action. These mAbs are exclusively recognized by CD16A (Fc?RIIIA) on NK cells, which is a low affinity Fc receptor. We have engineered NK cells expressing a novel chimeric Fc receptor that binds tumor-targeting mAbs with high affinity and induces robust ADCC. Advantages of this approach is that the engineered NK cells can bind to a broad array of therapeutic mAbs, which serve as diverse targeting elements for various tumor antigens and malignancies.

5:00 Generation of Engineered Pluripotent Cell-Derived T Cells as a Cornerstone Approach for Off-the-Shelf Cancer Immunotherapy

Bob Valamehr, PhD, MBA, Vice President, Cancer Immunotherapy, Fate Therapeutics

Pluripotent stem cell technology represents a unique and 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 therapeutic cells. I discuss our progress towards translating a unique and effective strategy to create a renewable source of “off-the-shelf” T cells derived from a single cell–derived master pluripotent cell line. Analogous to biopharmaceutical drug product development, the derived master pluripotent cell line is banked, characterized and repeatedly applied to our stage-specific directed differentiation process to reproducibly and reliably generate T cells. Preclinical data highlight the therapeutic value of pluripotent-derived T cells including anti-tumor capacity, manufacturing reliability and preclinical efficacy.

5:30 Dinner Short Course Registration*

*Separate registration required.

5:30 Close of Adoptive T Cell Therapy 1: Discovery

6:00-9:00 pm Dinner Short Course

SC3: Next-Generation Immunotherapies: Part 2

Day 1 | Day 2 | Download Brochure
Speaker Biographies | Participating Companies | Emerging Company Showcase Presenters