Cambridge Healthtech Instituteの第13回年次

Antibodies for Cancer Therapy
(がん治療のための抗体)

ブレークスルーセラピーの促進

2023年5月15〜16日 EDT(東部夏時間)

モノクローナル抗体のがん療法クラスでの成功は、抗体フラグメント/スキャフォールド、二重特異性/多重特異性抗体、抗体薬物複合体、免疫サイトカインなど、さまざまなタイプの抗体医薬の開発をもたらしました。それと同時に、がんに対する有望な免疫療法のアプローチとして、細胞ベースの治療法が浮上しています。「がん治療のための抗体」カンファレンスでは、講演者を招いてメカニズム、エンジニアリング、前臨床から臨床への移行、併用戦略について議論し、治療アプローチの最新かつ最も話題の情報を紹介することを目的としています。

5月14日(日)

- 5:00 pm Main Conference Registration1:00 pm

Recommended Pre-Conference Short Course2:00 pm

SC3: In silico and Machine Learning Tools for Antibody Design and Developability Predictions

 *Separate registration required. See short courses page for details.

5月15日(月)

Registration and Morning Coffee7:00 am

ANTIBODIES IN DEVELOPMENT - WHAT'S HOT & PROMISING?
開発における抗体 - 人気かつ有望なものは何か?

8:20 am

Chairperson's Opening Remarks

Daniel Chen, MD, PhD, Founder, Engenuity Life Sciences

8:30 am KEYNOTE PRESENTATION:

Antibody Therapeutics in Early Clinical Development: Format, Target, and Disease Trends

Janice M. Reichert, PhD, Chief Operating Officer, The Antibody Society

While trends in the global commercial late-stage clinical pipeline of antibody therapeutics are well documented, trends for the early-stage pipeline are difficult to ascertain because of the difference in scale - the late-stage and early-stage pipelines include ~150 and ~1100 molecules, respectively. This presentation will reveal recent trends in the formats and targets for antibody therapeutics in Phase I or II clinical studies, as well as the patient populations evaluated.

9:00 am

Cytotoxic PD-L1/PD-L2 Dual-Specific Antibodies Effectively Treat Both Immune “Hot” and “Cold" Cancers

Michael A. Curran, PhD, Founder and SAB Chairman, Immunogenesis; Associate Professor, Immunology, MD Anderson Cancer Center

We created novel fully human dual-specific antibodies that both block both PD-L1 and PD-L2 with high affinity and target PD-Ligand cells for depletion via ADCC and ADCP. The lead antibody outperforms PD-1 blockade across both "hot" and "cold" cancers through a unique combination of stromal depletion, complete PD-1 circuit blockade, and direct anti-tumor cytolysis. These antibodies appear safe in both mice and primates are moving into Phase I.

9:30 am Combining Innovative Technologies to Overcome Multiple Challenges of Neutralizing Antibody Discovery in Cancer Therapy

Shona GRAY-SWITZMANN, MSc, Account Manager, Monoclonal Antibodies, ProteoGenix

Though Phage Display has been instrumental in therapeutic antibody development, new challenges have appeared. Neutralizing antibodies can be difficult to obtain from naive human libraries due to lower affinity & self-tolerance. Combining innovative technologies such as Phage Display libraries supplemented with disease specific patient samples, NGS, AI & humanized mice for single B-cell sorting maximizes the chances of identifying neutralizing antibodies against any target, in particular for autoimmune disorders & cancer.

9:45 am Native Complex Membrane Antigen Expression on Poxvirus for Antibody Discovery

Ernest Smith, Senior VP, Research and CSO, Vaccinex Inc.

Vaccinex has developed a fusion protein technology to enable the direct incorporation of multi-pass membrane proteins into the membrane of poxviruses. The protein of interest is correctly folded and expressed in the cell-derived viral membrane and does not require any detergents or refolding before downstream use. Antigen expressing virus can be readily purified and used for antibody selection using any in vitro display platform or antibody generation in vivo.

 

Networking Coffee Break10:00 am

10:30 am

Anti-CCR8 Mediated Treg Cell Depletion for the Treatment of Solid Tumor Indications: Preclinical PKPD and Translational Strategy

Gautham Gampa, PhD, Principal Scientist, Preclinical & Translational PKPD, Genentech, Inc.

Regulatory T (Treg) cells represent a major immunosuppressive cell type in tumors and targeted depletion of tumor resident Treg cells can be a promising therapeutic approach to restore anti-tumor immunity. We have developed a human IgG1 antibody to preferentially eliminate CCR8-expressing Treg cells in tumor microenvironment through ADCC. The preclinical PK/PD findings and the methods used for translation to the clinic, including the selection of First-in-Human (FiH) dose, to inform the Phase I study design will be presented. 

11:00 am

Targeting of a Cancer-Associated LYPD3 Glycoform for Tumor Therapy

Patrik Kehler, CSO, Glycotope GmbH

We have developed an antibody which binds to tumor-associated LYPD3 in an O-glycosylationdependent manner and shows superior tumor specificity compared to conventional protein-binding anti-LYPD3 antibodies. The specificity of our antibody for glycosylated LYPD3 was determined using differentially glycosylated proteins in an ELISA format and confirmed using cell lines with specific glycosylation patterns as well as tumor cell lines expressing varying levels of LYPD3. Furthermore, binding to healthy and tumor tissues was analyzed by immunohistochemistry.

11:30 am LUNCHEON PRESENTATION:A Humanized Chicken Antibody Platform that Delivers Diverse and Developable Therapeutic Candidates

Ross Chambers, PhD, Vice President of Antibody Discovery, Integral Molecular

Highly conserved proteins frequently represent valuable, yet elusive, targets for antibody discovery due to immune tolerance across mammalian hosts. We discuss how chicken immunizations solve this problem and deliver antibodies with broad epitope coverage and long HCDR3 regions able to access functional pockets. Our chicken-based discovery platform includes technology for simultaneous humanization and affinity maturation and has produced high-affinity, highly developable antibodies against conserved targets including claudin 6, CCR8 and GLUT4.

12:00 pm LUNCHEON PRESENTATION:Luncheon Presentation to be Announced

Bruce Adams, PhD, Staff Scientist, 10x Genomics

Join us to learn how 10x Genomics Chromium Single Cell 5’ Barcode Enabled Antigen Mapping (BEAM) empowers rapid discovery of antigen-specific B-cell (BEAM-Ab) and T-cell (BEAM-T) clonotypes with unparalleled cellular characterization. Built on the proven Chromium Single Cell Immune Profiling workflow, BEAM enables screening of BCRs/TCRs against putative antigens in conjunction with gene expression, V(D)J sequencing, and cell surface protein expression.

INTERACTIVE DISCUSSIONS
インタラクティブディスカッション

12:30 pmFind Your Table and Meet Your Moderator
12:45 pmInteractive Discussions

Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussions page on the conference website for a complete listing of topics and descriptions.

INTERACTIVE DISCUSSION:

How to Discover Antibodies Against Novel/Difficult Targets

Horacio G. Nastri, PhD, Associate Vice President, Biotherapeutics, Incyte Corporation

  • What makes a target particularly difficult?
  • How to evaluate the challenges
  • Selection of therapeutic modality
  • Selection of optimal discovery strategy
  • Screening alternatives
INTERACTIVE DISCUSSION:

Failures and Successes in TNFRSF Agonist Antibody Drugs, and Future Outlook

Jieyi Wang, PhD, Founder & CEO, Lyvgen Biopharma

  • Mechanisms of action of TNFRSF agonistic antibodies
  • Lessons learned in the clinic
  • FcγR2B and tumor targeted conditional agonisms
  • New clinical developments to watch

Session Break1:30 pm

ANTIBODIES IN DEVELOPMENT (CONT.)
開発における抗体(続き)

1:45 pm

Chairperson's Remarks

Horacio G. Nastri, PhD, Associate Vice President, Biotherapeutics, Incyte Corporation

1:50 pm

INBRX-109: A Tetravalent Antibody Precisely Engineered for Optimal DR5 Agonism and Safety

Katelyn M. Willis, PhD, Associate Director, Biotherapeutics, Inhibrx, Inc.

INBRX-109 is a precisely engineered tetravalent agonist of death receptor 5. Designed to achieve a best-in-class therapeutic index, INBRX-109 induces robust apoptosis of cancer cells in vitro and in vivo while sparing healthy tissues. INBRX-109 was well tolerated and had anti-tumor activity in unresectable/metastatic conventional chondrosarcoma in a phase I study and is currently being evaluated in a blinded, placebo-controlled pivotal phase II trial.

2:20 pm

Developing a CD8+ T Cell Epitope-Delivering Antibody

Yong-Sung Kim, PhD, Professor, Molecular Science & Technology, Ajou University, Korea

Redirecting preexisting virus-specific cytotoxic CD8+ T lymphocytes (CTLs) to tumors by simulating viral infection of the tumor cells has great potential for cancer immunotherapy. In this talk, I will present a CTL epitope-delivering antibody, termed a TEDbody, engineered to deliver a viral MHC-I epitope peptide into the cytosol of target tumor cells by fusion with a tumor-specific cytosol-penetrating antibody for the recognition and lysis by virus-specific CTLs.

2:50 pm Talk Title to be Announced

Speaker to be Announced

Networking Refreshment Break3:20 pm

Transition to Plenary Keynote Session3:50 pm

PLENARY KEYNOTE SESSION
プレナリーセッション・基調講演

4:00 pm

Plenary Keynote Introduction

Adrian Bot, MD, PhD, CSO, Executive Vice President, R&D, Capstan Therapeutics

4:10 pm

Advances in CAR T Therapy

Carl H. June, MD, Richard W. Vague Professor in Immunotherapy; Professor of Medicine; Director, Center for Cellular Immunotherapies; Director, Parker Institute for Cancer Immunotherapy, University of Pennsylvania Perelman School of Medicine

Advances in the understanding of basic immunology have ushered in two major approaches for cancer therapy over the past 10 years. The first is checkpoint therapy to augment the function of the natural immune system. The second uses the emerging discipline of synthetic biology and the tools of molecular biology and genome engineering to create new forms of engineered cells with enhanced functionalities. The emergence of synthetic biology approaches for cellular engineering provides a broadly expanded set of tools for programming immune cells for enhanced function. Barriers to therapy of solid tumors will be discussed.

4:55 pm

The Next Frontier in Machine Learning and Biologics: "Lab in a Loop" Large Molecule Drug Discovery, From Optimization to de novo Discovery

John Marioni, PhD, Senior Vice President and Head of Computation, Research and Early Development, Genentech

A key opportunity in applying machine learning to augment biologic drug discovery and development is through constant iteration - a process we call "lab in a loop." By developing integrated methods for optimizing affinity and multiple developability parameters, as well as a close integration of antibody engineering, machine learning, and structural biology, we have the potential to more rapidly identify and test novel candidate molecules. Sophisticated machine learning frameworks allow us to integrate later stages of optimization into the earliest stages of discovery, while high-throughput experimental systems allow rapid improvement of all methods and molecules. This process starts with the integration of people and scientific culture and ends with tightly integrated computational and experimental systems.

Welcome Reception in the Exhibit Hall with Poster Viewing5:40 pm

Close of Day7:00 pm

5月16日(火)

Registration and Morning Coffee8:00 am

NON-TRADITIONAL ANTIBODY & BEYOND APPROACHES
非従来型の抗体とその他のアプローチ

8:25 am

Chairperson's Remarks

Daniel A. Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor, Therapeutic Radiology, University of Minnesota Masonic Cancer Center

8:30 am

Moxetumomab-Rituximab to Eliminate Minimal Residual Disease in Hairy Cell Leukemia

Robert J. Kreitman, MD, Chief Clinical Immunotherapy, Lab of Molecular Biology, NIH NCI

Complete remissions in hairy cell leukemia (HCL) with anti-CD22 recombinant immunotoxin Moxetumomab Pasudotox (Moxe) are more durable if minimal residual disease (MRD) negative, but anti-drug antibodies (ADA) can limit the effectiveness of the consolidation cycles needed to eliminate MRD.   To prevent ADA, Rituximab or Ruxience was added to Moxe (MoxeR) and 9 (64%) of 14 evaluable patients so far achieved MRD-free CR. ADA was less frequent than Moxe alone historically.

9:00 am

NK Cell Therapy for Cancer, from Individual to Off-the-Shelf CAR-Targeted NK Cells

Jeffrey Miller, MD, Deputy Director, Masonic Cancer Center; Professor of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota

Donor NK cells can induce complete remissions in patients with refractory leukemia. However, limitations include lack of persistence and specificity. Off-the-shelf NK cells from induced pluripotent stem cells (iPSC) containing multiple gene edits will promote specificity, persistence, and enhanced activity in vivo to enhance cancer therapy. While Chimeric Antigen Receptors (CARs) are best validated in B cell malignancies, strategies targeting B7-H3 in solid tumors will be discussed.

9:30 am

STK-012: An Engineered Selective IL2 Mutein That Promotes Anti-Tumor Responses without Related Toxicities

Patrick J. Lupardus, PhD, Vice President, Research & Head, Protein Sciences, Synthekine, Inc.

Interleukin-2 (IL-2) potently stimulates the proliferation, survival, and cytotoxicity of T and NK cells making it an attractive candidate for cancer immunotherapy. However, severe toxicities have limited its clinical utility. We have developed STK-012, an IL-2-agonist mutein selective for cells expressing the high affinity, trimeric IL-2 receptor (IL-2Ra/b/g) such as activated T cells. STK-012 preferentially stimulates tumor-specific T cells without significantly activating NK cells thus facilitating prolonged treatment without acute toxicity.

10:00 am Accelerating the Development of Novel Antibody-Drug Conjugates Through Site-Specific Conjugation Methods

An Ouyang, PhD, Product Manager, Product Development, ACROBiosystems

Antibody-drug conjugates are a class of potent, highly targeted anti-cancer therapeutics. However, developmental factors can affect the efficacy of ADCs, including payload, linker stability, and the conjugation method. In this study, we utilize our AGLink site-specific conjugation kit to perform site-specific enzymatic modification of IgG Fc glycans and further evaluate homogeneity and cytotoxicity.

Coffee Break in the Exhibit Hall with Poster Viewing10:30 am

11:10 am

Stability-Engineered, Half-Life Extended IL-18 for Cancer Immunotherapy

Travis W. Bainbridge, Scientist 4, Large Molecule Drug Discovery, Genentech, Inc.

IL-18 is a pro-inflammatory cytokine that promotes CD8+ T cell and NK cell effector function, enhancing intratumoral cytotoxicity. To date, clinical trials of recombinant IL-18 have demonstrated safety, but a lack of efficacy alone, or in combination with anti-cancer agents. The wild-type cytokine is challenging to produce, unstable, and cleared rapidly from circulation. We engineered a stabilized, half-life extended version of IL-18 and will be sharing pre-clinical in vivo results.

11:40 am

XTEN Polypeptide-Masked Protease Activated T Cell Engagers: XPAT Proteins - A Novel Format to Mitigate On-Target, Off-Tumor Problem

Volker Schellenberger, PhD, President & CEO, Amunix

XPAT proteins are conditionally active T cell engagers (TCEs) designed to exploit the dysregulated protease activity in tumors. In preclinical studies across multiple tumor targets, XPAT proteins demonstrated 1) strong masking of in vitro cytotoxicity by up to 4 logs; 2) potent in vivo efficacy at doses similar to the efficacious doses of unmasked TCE controls; and 3) masking increases tolerated Cmax in NHP by greater than 400-fold for HER2-XPAT.

12:10 pm

Designing Butyrophilin-Based Heterodimeric Gamma Delta T Cell Engagers for Immunotherapy

Suresh De Silva, PhD, CSO, GALDEN Platform, Shattuck Labs, Inc.

The ability to bridge the innate and adaptive arms of the immune system coupled with their capacity to recognize tumor cells independent of MHC makes gamma delta T cells an attractive target for cancer immunotherapy. The engineering and therapeutic potential of a butyrophilin 2A1 and 3A1 protein-based engager platform (GADLEN) that offers a novel approach to activate the Vg9Vd2 T cell subset for targeted killing of tumor cells will be presented.

12:40 pm Luncheon Presentation ILuncheon Presentation to be Announced

Speaker to be Announced

Luncheon Presentation II (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own1:10 pm

Close of Antibodies for Cancer Therapy Conference1:40 pm

Recommended Dinner Short Course6:30 pm

SC6: Developability of Bispecific Antibodies

*Separate registration required. See short courses page for details.

* 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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