Targeting Immune Cells for Emerging Immunotherapies

Strategies for Engaging T Cells, Gamma Deltas, NK and Macrophages

January 18 - 19, 2022 ALL TIMES PST

Immunotherapy has been an incredibly effective approach to engaging one’s own immune system to combat many types of cancer. Recently, astounding new strategies have been employed to overcome the remaining obstacles, including targeting solid tumors, “cold” tumors that until now have been resistant to immunotherapy, and addressing the need for “off-the-shelf” therapies. The repertoire of immune cells being engaged have expanded beyond T cells engagers to gamma deltas, NK cells, macrophages and strategies for targeting the entire tumor ecosystem or microenvironment. Come hear from the world’s leading experts on employing the latest innovative approaches and clinical results.

Tuesday, January 18

1:00 pm Registration (Sapphire West Foyer)
1:30 pm Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)


Session Room: Sapphire L

2:00 pm Organizer's Welcome Remarks

Christina C. Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute

2:05 pm

Chairperson's Remarks

Paul Parren, PhD, Executive Vice President, Lava Therapeutics; Professor, Leiden University Medical Center
2:10 pm

Novel Chimeric Antigen Receptor T Cell Therapies for Advanced Prostate Cancer: Recent Clinical Trials (and Tribulations)

Vivek Narayan, MD, Assistant Professor, Hematology Oncology, University of Pennsylvania

Therapeutic progress has thus far been limited with cellular therapies in advanced solid tumors, due to limited observed efficacy and treatment-related toxicities. Advanced prostate cancer represents a compelling model for CAR T therapy. We will review current mechanisms and rationale for re-directed T cell therapies for advanced prostate cancer; describe an early experience with CAR T therapy for advanced prostate cancer; and discuss challenges and future approaches for prostate cancer CAR T therapy.

2:40 pm

PSMA-Directed CAR T Cell Platforms – Can We Maximize Efficacy to Improve PSMA Targeting?

Susan F. Slovin, PhD, Medical Oncologist, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center

Prostate cancer is first solid tumor with an approved autologous immunotherapy with a survival benefit. This treatment has had limited impact on the biomarker, Prostate Specific Antigen (PSA) with minimal antitumor effects. Prostate cancer remains suboptimally responsive to other immunologic approaches including checkpoint inhibitors, or vaccines but with some activity seen using bispecific T cell engagers (BiTEs) and Chimeric Antigen Receptor (CAR) T cells. Strategies to improve the conversion of what is deemed as an immunologically “bland” microenvironment to one that is immunologically “hot” is the focus for PSMA-directed CARs in patients with metastatic castration resistant prostate cancer (mCRPC).

3:40 pm Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
4:30 pm

Human Costimulatory Bispecific Antibodies in Cancer Immunotherapy: Focus in Prostate Cancer

Dimitris Skokos, PhD, Senior Director, Cancer Immunology, Regeneron Pharmaceuticals

T cell activation is initiated upon binding of the T Cell Receptor (TCR)/CD3 complex to peptide-MHC complexes (“signal 1”); activation is then enhanced by engagement of a second “co-stimulatory” receptor, such as CD28 on T cells binding to its cognate ligand(s) on the target cell (“signal 2”). However, tumors evade the immune system often by downregulating one or both of these signals 1 and 2. We developed a class of bispecific antibodies that mimic signal 2, by bridging a second tumor associated antigen (TAA) to CD28 on T cells. Combining this novel class of co-stimulatory bispecific antibodies with PD-1 mAb or the emerging class of TAAxCD3 bispecifics may provide well-tolerated, “off-the-shelf” antibody therapies with potentially enhanced anti-tumor efficacy.

5:00 pm

Bispecific Gamma-Delta T Cell Engagers Targeting PSMA for the Treatment of Prostate Cancer

Paul Parren, PhD, Executive Vice President, Lava Therapeutics; Professor, Leiden University Medical Center

The development of next-generation bispecific gamma-delta T cell engagers (bsTCE) with a widened therapeutic window characterized by high potency and high tumor selectivity has strong potential. Lava Therapeutics’ platform is based on the selective recruitment of  Vγ9Vδ2 T cells for eradicating tumor cells. This presentation will discuss our bsTCEs designed to engage Vγ9Vδ2 T cells against tumor cells expressing PSMA for the development of novel therapeutics in prostate cancer.

5:30 pm Close of Day

Wednesday, January 19

7:30 am Registration (Sapphire West Foyer)
8:00 am BuzZ Sessions with Continental Breakfast (Sapphire Foyer)

PepTalk BuzZ Sessions are focused, stimulating discussions in which delegates discuss important and interesting topics related to upstream protein expression and production through downstream scale-up and manufacturing. This is a moderated discussion with brainstorming and interactive problem-solving between scientists from diverse areas who share a common interest in the discussion topic. Continue to check the event website for detailed discussion topics and moderators.


Session Room: Sapphire L

9:00 am

Chairperson's Remarks

Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute
9:05 am

Developing EBV-Specific Allogeneic T Cell Immunotherapies for a New Tomorrow

Jakob Dupont, MD, Global Head, R&D, Atara Biotherapeutics

Autologous T cell therapies have been life-changing for many patients; but virus-specific, allogeneic platforms hold the promise of effective, off-the-shelf treatments manufactured at scale, and delivered to patients within days. In this talk, the flexibility and advantages of EBV T cells and how allogeneic treatments may change the treatment paradigm for cancer and autoimmune diseases will be discussed.

9:35 am

Efficient NK Cell Redirection by Triggering NKp30

Stefan Zielonka, PhD, Associate Director, Protein Engineering & Antibody Technologies, Merck KGaA

Activating NK cell receptors represent promising target structures to elicit potent anti-tumor immune responses. We have generated efficient NK cell engagers that bridge Natural Cytotoxicity Receptor NKp30 on NK cells with EGFR on tumor cells in several multifunctional IgG-like bispecific formats. In this talk I will discuss different strategies for targeting NKp30.

Nicholas Abuid, PhD, Application Scientist, ACROBiosystems

Transmembrane proteins (TPs) are embedded in the cell membrane and span the intracellular and extracellular environments. The transmembrane region directly interacts with the phospholipid bilayer and is an important channel bridging these environments enabling transport of various ions and molecules and relaying activation and response reactions to extracellular stimuli. These reactions propagate intracellularly through downstream signaling pathways and regulate cell metabolism, cellular activity, and cellular fate. TPs have broad applications in cancer immunotherapy and autoimmune diseases. Our team has engineered methods to formulate TPs to support research in understanding the role of various diseases.

10:35 am Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:15 am

CAR-M: Engineered Macrophages for Cancer Immunotherapy 

Sascha Abramson, PhD, Vice President, Scientific Operations, Carisma Therapeutics

Adoptive cell therapies have demonstrated remarkable outcomes in hematologic malignancies, but efficacy in solid tumors is still lacking. We have established a novel, proprietary monocyte and macrophage based cell therapy platform based on chimeric antigen receptor macrophages (CAR-M). In this talk we will review the CAR-M platform, present novel preclinical data, and discuss the ongoing Phase I, first-in-human CAR-M trial for HER2+ metastatic solid tumors.

11:45 am

Innovative Translational CAR NK Cell Engineering

Tamara J. Laskowski, PhD, Senior Director, Head, Clinical Development, Personalized Medicine, Lonza Global

Advancements in cellular engineering have led to the development of novel strategies aimed at overcoming current challenges. In this presentation, we will discuss the advantages of allogeneic NK cells as a resource for cell therapy. We will focus on strategies to leverage the intrinsic anti-tumor properties of NK cells, and will discuss our work to develop novel approaches to enhance NK function and persistence though genetic engineering.

12:15 pm Enjoy Lunch on Your Own
1:25 pm Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing (Sapphire Ballroom)


2:15 pm

Chairperson's Remarks

Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute

Chimeric Antigen Receptor-Modified Immune Effector Cell Therapies: Learning from the Present; Charting a Path to the Future

Renier J. Brentjens, MD, PhD, Deputy Director and Chair, Department of Medicine, Roswell Park Comprehensive Cancer Center

T cells can be genetically engineered to target tumor associated antigens through the expression of a chimeric antigen receptor (CAR). CAR T cells have demonstrated marked clinical outcomes in several hematologic malignancies and yet, many patients either fail to respond or relapse after an initial response. We have developed a novel platform, armored CAR T cells, wherein T cells are further engineered to enhance CAR T cell anti-tumor efficacy as well as persistence. Several approaches will be addressed.

2:50 pm

Hypoxia-Sensing CAR T Cells Avoid Systemic Toxicity to Focus the Fight on Solid Malignancies

James N. Arnold, Lecturer, Cancer Cell Biology & Imaging, Kings College London

Tumor-selective antigens to direct CAR binding are scarce for treating solid malignancies. However, tumor selectivity is crucial as on-target off-tumor activation of CAR T cells can result in potentially lethal toxicities. We have engineered a stringent oxygen-sensing system ‘HypoxiCAR’ which restricts CAR expression to hypoxic microenvironments, such as is found in solid tumors. In preclinical models, HypoxiCAR T cells provide robust anti-tumor efficacy while avoiding systemic toxicities associated with on-target off-tumor activation.


3:20 pm

Developing Allogeneic Vd1 (γδ) T Cell Therapies

Oliver Nussbaumer, PhD, Founder & Vice President, Immunology, GammaDelta Therapeutics, Ltd.

GammaDelta Therapeutics is developing allogeneic cell therapy platforms based on Vd1 (γδ) T cells. We are exploiting the biology and characteristics of these unconventional T cells to progress differentiated products for adoptive cell therapy of hematologic malignancies and solid tumors.

3:50 pm

CD8ab CAR T Cell Development from TiPSC

Sjoukje van der Stegen, PhD, Research Fellow, Memorial Sloan Kettering Cancer Center

T cell-derived induced pluripotent stem cells (TiPSCs) provide a powerful platform for unlimited production of specific T cells. Initial differentiation platforms facilitated development of innate-like T lymphocytes. Through careful adjustment of the Notch and ITAM signaling, we can facilitate alpha-beta T lineage commitment, while utilizing the CAR to drive the cells through T cell development and maturation.

4:20 pm

Off-the-Shelf, CD30, CAR-Modified EBV-Specific T Cells for the Treatment of CD30-Positive Lymphoma

Cliona M. Rooney, PhD, Professor, Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine

Banked, allogeneic therapeutic T-cells overcome problems related to manufacturing failures of patient derived products, the length of time for manufacture and testing of products, product potency and expense, and are the holy grail for cellular Immunotherapy. Major problems that beset allogeneic T-cells are graft versus host disease and graft rejection mediated by donor- and host-derived alloreactive T-cells respectively. We are using banked EBV-specific T-cells (EBVSTs) modified to express a CD30.CAR for the treatment of allogeneic patients with CD30-positive lymphoma with impressive clinical responses. The use of EBVSTs solves the problem of GVHD, since with their more limited TCR repertoire, EBVSTs have not cause GVHD in hundreds of allogeneic recipients, while host alloreactive T-cells upregulate CD30 on stimulation, so that they can be eliminated by the CD30.CAR, thus preventing rejection.

4:50 pm Close of Conference