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Cambridge Healthtech Institute’s 6th Annual

Engineering Next-Generation Cancer Immunotherapies
( 次世代癌症免疫疗法的开发 )

New Protein Engineering Science to Support the Development of Novel Immunotherapeutics and Treatment Combinations

1月20日~21日

Part of the Antibody Therapeutics pipeline

Based on the clinical successes of checkpoint inhibitors, the industry is now directing its attention to combination treatments, single agent therapeutics with multiple modes of action, confronting resistance mechanisms, reducing toxicity and the persistent challenge of solid tumors. Cambridge Healthtech Institute’s 6th Annual Engineering Next-Generation Cancer Immunotherapies conference provides a forum in which research scientists can discuss the contributions of protein engineering to the discovery and development of novel biotherapeutics in the IO space.

Final Agenda

1月19日(日)

4:00 - 6:00 pm Pre-Conference Registration

1月20日(一)

7:00 am Registration and Morning Coffee

Discovery of IO Combinations

9:00 Organizer’s Welcome Remarks

Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute

9:05 Chairperson’s Opening Remarks

Govinda Sharma, PhD, Postdoctoral Fellow, Genome Sciences Center, BC Cancer Research Center, Canada

KEYNOTE PRESENTATION

9:10 Defining T Cell States Associated with Response to Combination Immunotherapy

Shahram Salek-Ardakani, PhD, Senior Director, Cancer Immunology Discovery, Pfizer

It has remained unclear how simultaneous blockade of PD-1 and costimulation of OX40 and 4-1BB receptors synergize for potent T cell-driven anti-tumor efficacy. Using high-dimensional analysis, we examined the dynamics of effector CD4 and CD8 T cell responses in the tumor microenvironment (TME) in response to anti-PD-1/OX40/4-1BB treatment. Our findings provide insight into T cell states and biomarkers that underlie the synergy between OX40/4-1BB agonism and PD-1 blockade.

9:50 Enhancing Tumor-Targeting Antibodies through CD27 Immunostimulation

Sean H. Lim, MBChB, PhD, Associate Professor, Haematological Oncology, Center for Cancer Immunology, University of Southampton, United Kingdom

Agonistic antibodies, such as those against the TNFR superfamily member, CD27, can be used to enhance the anti-tumor efficacy of direct targeting antibodies through bystander myeloid cell activation. Here, we will present our recent data on the factors that govern the potency of CD27 agonistic antibodies.

10:20 Networking Coffee Break

Engineering Considerations for New IO Modalities

10:45 Engaging Multiple T Cell Targets with Bispecific Antibodies for Selective Immune Stimulation in the Tumor Microenvironment

Michael Hedvat, PhD, Group Leader, Cell Biology, Xencor

The XmAb® bispecific platform has enabled clinical development of TIL-targeting agents, including XmAb20717 (combining PD1 and CTLA4 blockade), XmAb22841 (CTLA4 and LAG3 blockade), and XmAb23104 (PD1 blockade with ICOS agonism). Xencor has also engineered an IL15/IL15Rα-Fc complex to create the clinical candidate, XmAb24306, thus establishing a tunable format for rapid generation of targeted immune activators. I will also discuss development of a TME-directed IL-15 achieved via coupling to an anti-PD1-moiety.

11:15 Directing T Cell Phenotype and Metabolism during Large-Scale Expansion

Kathryn Henckels, PhD, Senior Scientist, Process Development, Amgen

T cell therapy involves treating patients with live T cells engineered to recognize tumor-specific antigens. Efficacy depends on persistence, which is mainly driven by T cell phenotype; an effector cell will quickly become exhausted, whereas a stem cell memory T cell-type can survive for months or years. A manufacturing process that controls the differentiation of T cells throughout the expansion process will result in a final product that is more efficacious.

11:45 Rapid Selection and Identification of Functional CD8+ T Cell Epitopes from Large Peptide-Coding Libraries

Govinda Sharma, PhD, Postdoctoral Fellow, Genome Sciences Center, BC Cancer Research Center, Canada

We have developed a novel methodology for high-throughput, function-based T cell epitope profiling that is capable of identifying T cell antigens from libraries of peptide-coding sequences much larger than would be feasibly tractable using conventional plate-based assays. Currently, we are mobilizing this technology towards performing unbiased neoantigen screenings for discovering novel targets of T cell immunotherapy and for assessing potential off-target cross-reactivity of designer TCR therapeutics.

12:15 pm Presentation to be Announced

12:30 Sponsored Presentation (Opportunity Available)

12:45 Session Break

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

Tumor Specificity and Regional Delivery

2:00 Chairperson’s Remarks

Mitchell Ho, PhD, Senior Investigator, National Cancer Institute, NIH

2:05 A Coiled-Coil Masking Domain for Selective Activation of Therapeutic Antibodies

Matthew Levengood, PhD, Principal Scientist, Protein Sciences, Seattle Genetics

To enhance the selectivity of monoclonal antibodies for tumors over healthy tissues, we have developed an antibody masking system that utilizes coiled-coil peptide domains to sterically impede antigen binding. On exposure to tumor-associated proteases, the coiled-coil domains can be cleaved and antibody function restored. The coiled-coil domain is a generalizable approach for antibody masking that results in antibody therapeutics with improved circulation half-lives, minimized systemic effects, and improved tumor targeting.

2:35 Novel Antibody Engineering to Improve the Therapeutic Index of Solid Tumor-Targeting Antibodies

Hitoshi Katada, PhD, Research Scientist, Biologics Discovery, Chugai Pharmaceutical Co., Ltd., Japan

One of the remaining issues of antibody therapeutics is on-target, off-tumor toxicity induced by binding to target antigens expressed in normal tissues. To overcome this problem, we have established novel antibody engineering to enable antibody binding to the antigen selectively at tumor site, but not at normal tissues.

3:05 Find Your Table and Meet Your BuzZ Session Moderator

3:15 BuzZ Sessions with Refreshments

Join your peers and colleagues for interactive roundtable discussions.

Click here for more details

Engineering Challenges for Novel CAR T Configurations and Combinations

4:30 GPC3 as a CAR T Cell Therapy Target in Cancer

Mitchell Ho, PhD, Senior Investigator, National Cancer Institute, NIH

In the past decade, we have studied the role of glypican-3 (GPC3) as a therapeutic target in hepatocellular carcinoma. We have created new CAR T cells based on our antibodies that are specific for the N-lobe and C-lobe of GPC3 and tested them in mice. Using single cell-based analysis, we have identified a small subset of polyfunctional T cells that exhibit highly persistent T cell expansion in the tumor microenvironment.

5:00 Small Molecule Regulated Antibodies for CAR T Cell Therapy

Javier Chaparro-Riggers, PhD, Executive Director, Biomedicine Design, Pfizer

CAR T cell therapy has shown clinical success against hematological malignancies, nevertheless frequently accompanied by diverse adverse events. To enhance the safety profile of CAR-T therapy, we developed a conditionally-activatable, single-module CAR architecture, in which the cytotoxicity is specifically modulated by a small-molecule drug. The resulting CAR-Ts demonstrated specific cytotoxicity of tumor cells comparable to a traditional CAR, but the cytotoxicity could be reversibly attenuated by the addition of the small-molecule.

5:30 Use of CD19-Directed CAR T Cells to Kill Any Tumor

Roy Lobb, PhD, Director and Cofounder, Aleta Biotherapeutics

We reprogram CAR T cells to CD19 (CAR19s) to kill any heme or solid tumor, using CD19 fused to an antibody fragment. Such CD19-binding proteins (CD19-BPs) can ‘coat’ any tumor and direct CAR19-dependent cytotoxicity while targeting two or more antigens with potency and selectivity. By placing the CD19-BPs within the CAR19 itself, the CAR19s secrete the CD19-BPs locally, providing ‘on-demand’ tumor killing combined with inherent long-term persistence.

6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing

7:15 Close of Day

1月21日(二)

8:15 am Registration and Morning Coffee

Targeting the Tumor Microenvironment with Therapeutic Proteins

8:45 Chairperson’s Remarks

Traian Sulea, PhD, Principal Research Officer, Human Health Therapeutics, National Research Council Canada

8:50 Reengineering the Physical Microenvironment of Tumors to Improve Treatment Response

Lance L. Munn, PhD, Associate Professor, Department of Radiation Oncology, Massachusetts General Hospital

As tumors grow in a confined space, fibrosis and unchecked proliferation result in a highly abnormal physical microenvironment. Tumor mechanopathologies, including increased tissue stiffness and accumulation of solid stresses, fuel tumor progression and treatment resistance by altering extracellular matrix (ECM) production and blood flow. Reengineering the tumor microenvironment to normalize the tumor vasculature and ECM can improve treatment and is already showing promise in the clinic.

9:20 Engineering pH-Dependent Antibody Binding for Selective Targeting of Solid Tumors

Traian Sulea, PhD, Principal Research Officer, Human Health Therapeutics, National Research Council Canada

Development of monoclonal antibodies as anti-cancer agents requires further optimization of their safety for use in humans. Among the optimization avenues for specific tumor targeting is the slightly higher acidity of solid tumors relative to normal tissues. A structure-based computational approach was applied here to engineer antibody fragments with selective binding in acidic environments relative to physiological pH. Designed, full-size antibodies exhibit binding selectivity between tumor and normal cell models.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Exploiting the ECM as a Therapeutic Target in Disease

Noor Jailkhani, PhD, Postdoctoral Research Scientist, Koch Institute for Integrative Cancer Research, MIT

To exploit the ECM as an imaging and therapeutic target, we developed recombinant single domain antibodies called “nanobodies” against disease-associated ECM proteins. We demonstrated their specificity for tumors, metastatic sites and early lesions by immuno-PET/CT imaging in multiple models of cancer. Their properties make nanobodies promising candidates for therapeutic applications and we showed that nanobody-based CAR T cells were able to inhibit the growth of solid tumors.

11:30 Epitope and Fc-Mediated Cross-Linking are Critical for MoA of 4-1BB Antibodies: Anti-Tumor Efficacy vs. Liver Toxicity

Hamsell Alvarez, PhD, Principal Research Scientist, Immuno-Oncology Discovery, AbbVie

4-1BB agonist antibodies have demonstrated potent anti-tumor activity, but cause severe hepatotoxicity in mouse models. We identified a new class of 4-1BB antibodies that bind unique epitopes, retain anti-tumor efficacy, and result in significantly less liver toxicity. T cell costimulation activity only occurs when these antibodies are crosslinked, and anti-tumor efficacy was lost in FcγRIIB-deficient mice. This highlights the importance of epitope and isotype selection and suggests that 4-1BB biotherapeutics with improved safety profiles can be developed.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Close of Engineering Next-Generation Cancer Immunotherapies Conference

 

5:45 - 8:45 Recommended Dinner Short Courses*

 

SC1: Best Practices for Biotherapeutic Discovery and Development

Instructor: Wasfi AlAzzam, PhD, CSO, TechnoPharmaSphere (TPS)

 

SC2: The Safety of Immunotherapy and ADCs: How to Mitigate Risk and Adverse Effects

Instructors:

Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen, LLC

George Octavian Badescu, PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG

 

*Separate registration required

* 活动内容有可能不事先告知作更动及调整。

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