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Cambridge Healthtech Institute 第5回

Engineering Next-Generation Cancer Immunotherapies
( 次世代がん免疫療法の開発 )

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

2019年1月14日~15日

 

次世代がん免疫療法の開発をテーマにしたこのカンファレンスプログラムは、研究者たちが腫瘍治療の分野における新たな生物学的製剤の創薬と開発に対してタンパク質工学がどのような形で貢献できるのか議論する場を提供します。

Final Agenda

1月13日(日)

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

1月14日(月)

7:00 am Registration and Morning Coffee

次世代免疫療法薬開発のための研究手段

9:00 Welcome by Conference Organizer

Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute

9:05 Chairperson’s Opening Remarks

John Williams, PhD, Professor, Department of Molecular Medicine, Beckman Research Institute; Member, Cancer Immunotherapeutics Program, City of Hope Comprehensive Cancer Center


KEYNOTE PRESENTATION

9:10 Integrative Pharmacology: Advancing Development of Effective Immunotherapies

Mohammad Tabrizi, PhD, Director, Biologics PPDM, Merck Research Laboratories Palo Alto

With the recent advances in cancer immunotherapy, it is now evident that the antigen-specific activation of the patients’ immune responses can be utilized for achieving significant therapeutic benefits. Due to the nature of immunotherapy, i.e., harnessing the patient’s immune system, it becomes critical to evaluate the important variables that can guide development and effective clinical dosing paradigms following single and combination therapies. Critical topics related to preclinical, translational and clinical development of IO agents are discussed.

9:50 T Cell Engaging Bispecific Antibodies: Comparing Pfizer’s Platforms

Javier Chaparro-Riggers, PhD, Senior Director, Protein Engineering, Pfizer

T cell engaging bispecific antibodies are a promising therapeutic approach for the treatment of multiple cancer types. A variety of formats are currently being tested in the clinic. Pfizer has developed several Fc-containing T cell engaging bispecific antibody platforms that increase the half-life and allow for conventional dosing. These platforms are currently evaluated in the clinic. Here, we will compare these platforms and the challenges and opportunities of each platform will be highlighted.

10:20 Networking Coffee Break

10:45 Development and Validation of Imaging Biomarkers for IO Applications

Michael Evans, PhD, Assistant Professor, Radiology and Biomedical Imaging, University of California, San Francisco

This presentation will outline recent efforts at UCSF to apply omics technologies and phage display to identify and target with recombinant human antibodies cell surface antigens that are upregulated by important oncogenic drivers. Recent screening efforts have identified new antibodies against cell surface proteins upregulated by mutant KRAS, c-MYC, and mTORC1, and the antibodies have been further matured for nuclear medicine applications like PET imaging and radioimmunotherapy.

11:15 Development of a New Patient Derived Xenograft Humanized Mouse Model to Study Human Specific Tumor Microenvironment and Immunotherapy

Qingfeng Chen, PhD, Principal Investigator, Institute of Molecular and Cell Biology, A*STAR, Singapore

Recently, we transplanted patient-derived xenograft tumors with type I human leukocyte antigen-matched human immune system in NOD-scid Il2rg-/- mice. Similar to patients, the human immune system in our model is educated by tumor and exhibits exhaustion phenotypes. Our model also demonstrates both therapeutic and side effects of immune checkpoint inhibitors. Thus, we provide a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.

11:45 Pritumumab, the Journey from the Bench to the Bedside

Mark C. Glassy, PhD, CSO, Nascent Biotech

Pritumumab, a natural human IgG1 kappa antibody recognizes an altered form of vimentin called ecto-domain vimentin (EDV) expressed on the surface of cancer cells. In a Phase II clinical trial with Japanese brain cancer patients, pritumumab showed an overall response rate of 25-30%. A recombinant version of pritumumab was made from CHO cells and is currently being prepared for additional FDA-approved clinical trials.

12:15 pm Sponsored Presentation (Opportunity Available)

12:45 Session Break

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

次世代チェックポイント阻害剤の開発

2:00 Chairperson’s Remarks

Yariv Mazor, PhD, Senior Scientist, Antibody Discovery & Protein Engineering, MedImmune, LLC

2:05 Checkpoint Inversion by INBRX-105: A Bispecific Multivalent PD-L1 x 41BB Single Domain Antibody Therapeutic Delivering Checkpoint Blockade and Conditional Immune Activation within the Tumor

John Timmer, PhD, Vice President, Research, InhibRx

InhibRx has developed a bispecific multivalent antibody with conditional 41BB agonist activity and potent PDL1 checkpoint blockade. This checkpoint inversion converts T cell suppressive PDL1 within the tumor into 41BB agonism driving anti-tumor T cell co-stimulation while avoiding toxicity from systemic 41BB activation. INBRX-105 is built from InhibRx’s proprietary single domain antibody platform and innovative therapeutic format. Potent preclinical efficacy combined with a clear safety profile have propelled INBRX-105 toward the clinic.

2:35 Development of the First Enzyme-Based Immune Checkpoint Inhibitor for Cancer Therapy

Christos Karamitros, PhD, Director, Protein Engineering, Aeglea Biotherapeutics

It is well established that kynurenine, a key intermediate metabolite of the tryptophan catabolic pathway, has very potent immunosuppressive properties. Current clinical approaches focus on the development of IDO1 and TDO inhibitors to impair kynurenine synthesis. However, our novel approach degrades kynurenine into non-toxic and immunologically inactive metabolites in order to relieve immune suppression in cancer. This work showcases the first enzyme-based immune checkpoint inhibitor.

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.

 

併用効果を有する二重特異性抗体と単剤

4:30 Design Meets Biology – Engineering a PD-1/CTLA-4 Bispecific Antibody to Improve Both Safety and Efficacy

Yariv Mazor, PhD, Senior Scientist, Antibody Discovery & Protein Engineering, MedImmune, LLC

MEDI5752 is a monovalent bispecific IgG1 antibody (DuetMab), targeting the two clinically validated receptors; PD-1 and CTLA-4. The bispecific antibody introduces novel MOAs that may provide an improved therapeutic index when compared to the two monotherapies and mAb combinations. MEDI5752 is currently being clinically evaluated for safety and efficacy.

5:00 Functionalization of mAbs Using Natural Amino Acids

John Williams, PhD, Professor, Department of Molecular Medicine, Beckman Research Institute; Member, Cancer Immunotherapeutics Program, City of Hope Comprehensive Cancer Center

Many disparate genetic and chemical approaches have been developed to leverage the exquisite specificity of antibodies for therapeutic and diagnostic intent. Here, we use the site-specific meditope interaction to catalyze the efficient formation of a disulfide bond without the need for incorporating non-natural amino acids or post-translational, enzymatic modifications. This ‘swappable’ platform permits the stable modification of antibodies through the exchange of meditopes functionalized to include imaging agents, cytotoxins and biologics.

5:30 Tumor Antigen-Dependent T Cell Activation and Tumor Localization Induced by a Novel 4-1BB x 5T4 ADAPTIR™ Bispecific Antibody

Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience AB, Sweden

ALG.APV-527 is designed to induce potent tumor specific CD8 T cell activation by activating 4-1BB on T cells only when simultaneously engaging 5T4 on tumor cells. Pre-clinical in vitro and in vivo data demonstrates that ALG.APV-527 stimulates increased T cell activation in the presence of 5T4-expressing cells, localizes to 5T4 positive tumors and inhibits tumor growth. This data supports its potential to provide effective tumor-directed immune activation with reduced systemic side effects.

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

7:15 Close of Day

1月15日(火)

8:00 am Registration and Morning Coffee

CAR-T細胞療法の開発にまつわる課題

8:30 Chairperson’s Remarks

Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience AB, Sweden

8:35 Application of Single Domain Antibody Technology in CAR-T Cells for Treating Solid Tumors

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

Single domain antibodies represent a very different class of molecules: small, easy to express, stable and capable of revealing buried epitopes unreachable by conventional antibodies. We have generated single domain antibodies that target tumor antigens (e.g. mesothelin, GPC3 and GPC2) and developed CAR T cells based on these antibodies. Construction and next-generation sequencing analysis of our new phage-displayed shark and camel single domain antibody libraries will also be described.

9:05 CAR-Ts and Combination Therapy with Checkpoint Blockade

Prasad S. Adusumilli, MD, Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center (CTC), Memorial Sloan-Kettering Cancer Center

In solid tumor immunotherapy, we have shown that regional administration of CAR T cells will have increased potency and decreased toxicity, and that exhausted PD-1 expressing CAR T cells can be functionally rescued by use of checkpoint blockade agents. We now have translated both concepts to clinical trials. The specifics of patient stratification for combination immunotherapy, evaluation parameters and outcomes interpretation are ongoing areas of clinical and translational investigation.

9:35 Sponsored Presentation (Opportunity Available)

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

11:00 Rewiring T Cell Responses to Soluble Factors with Chimeric Antigen Receptors

Yvonne Chen, PhD, Assistant Professor, Chemical & Biomolecular Engineering, UCLA

Immunosuppression in the tumor microenvironment presents a critical barrier to chimeric antigen receptor (CAR)-T cell therapy for solid tumors. Here, we discuss the development of CARs that respond to soluble antigens in general and the immunosuppressive cytokine TGF-β in particular. The development of CAR-T cells that can convert soluble immunosuppressive factors into potent T cell stimulants offers a new approach to engineering effective CAR-T cell therapies for solid tumors.

11:30 Development of a Universal CAR-T Cell Targeting System

Mauro Castellarin, PhD, Postdoctoral Researcher, Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine

CAR T cell (CART) targeting of solid tumors is hindered by heterogeneous tumor clones with diverse antigen profiles. To counter this, we developed a universal CAR that can attach to different antigen recognition molecules and enables CARTs to kill a diverse set of tumor cells. This is a promising new advancement as it allows CART treatment to adapt to changes in the tumor landscape throughout the course of the disease.

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: Introduction to CAR-T Engineering for Protein Scientists

SC2: Structure-Based Optimization of Antibodies

SC4: Immunogenicity for Biologics

Click here for more details.

*Separate registration required

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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