Cambridge Healthtech Institute's Eighth Annual

Antibodies for Cancer Therapy

( 癌症治疗抗体 )

Winning Strategies for the Next Breakthrough Therapies

2018年4月30日-5月1日 | World Trade Center | 马萨诸塞州波士顿

 

The specificity of antibodies makes them an ideal weapon against cancer. Novel antibody constructs are advancing rapidly through discovery to preclinical and clinical development with greater selectivity for specific cell populations and potency. The Eighth Annual Antibodies for Cancer Therapy meeting has become a pivotal forum for reviewing the newest trends in design of novel constructs, emerging target investigation, preclinical and clinical data assessment and latest approaches for selective targeting.

 

Scientific Advisory Board

Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital

Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH

Horacio G. Nastri, PhD, Senior Director, Antibody Biotherapeutics, Incyte Corporation

 

  Final Agenda

Sunday, April 29

Recommended Short Course(s)*

SC2: Translational Considerations for Development of Monoclonal Antibodies and Emerging Constructs: Part I: Focus on Construct Design

Glareh Azadi, PhD, Senior Scientist, Translational PKPD, Merck Research Laboratories

Gadi Bornstein, PhD, Senior Director, Biologics Discovery, TESARO, Inc.

Veronica Juan, PhD, Principal Scientist, Protein Sciences, Merck Research Labs

Scott L. Klakamp, PhD, Vice President of Chemistry and Biochemistry, Bioptix

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

SC7: Translational Considerations for Development of Monoclonal Antibodies and Emerging Constructs: Part 2: Focus on Preclinical Development

Glareh Azadi, PhD, Senior Scientist, Translational PKPD, Merck Research Laboratories

Gadi Bornstein, PhD, Senior Director, Biologics Discovery, TESARO, Inc.

Veronica Juan, PhD, Principal Scientist, Protein Sciences, Merck Research Labs

Scott L. Klakamp, PhD, Vice President, Chemistry and Biochemistry, Bioptix

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


*Separate registration required.

MONDAY, APRIL 30

7:00 am Registration and Morning Coffee

SELECTING EMERGING TARGETS

8:30 Chairperson's Remarks

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


8:40 Immunotherapy for Liver Cancer: How and Targeting What?

Tim GretenTim F. Greten, MD, Senior Investigator, GI Maligancy Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute

Hepatocellular carcinoma (HCC) is the sixth most frequent neoplasm and the second leading cause of cancer-related deaths worldwide. HCC typically arises in the context of liver cirrhosis caused by viral infection, environmental factors, toxins, and in rare cases genetic conditions. We have been studying how the tumor microenvironment affects anti-tumor immunity and study novel immune based treatment approaches for the treatment of patients with liver cancer.

9:10 Improving Cancer Therapy through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature

Bradley CroixBradley St. Croix, PhD, Senior Associate Scientist, Head, Tumor Angiogenesis Unit, Mouse Cancer Genetics Program, National Cancer Institute

CD276 is frequently overexpressed in tumors on both tumor cells and tumor infiltrating blood vessels that fuel its growth, making it an alluring dual compartment target for an ADC therapy. The development of anti-CD276 ADCs armed with MMAE or PBD will be discussed, along with the mechanistic basis for the differential efficacy of these agents against tumor-associated stroma and implications for development of other vascular-targeted ADCs.

9:40 Pharmacological Characterization of Anti-Glypican 3/CD3 Bispecific T Cell-Redirecting Antibody ERY974

Junichi NezuJunichi Nezu, PhD, Senior Specialist, Project & Lifecycle Management Unit, Chugai Pharmaceutical, Co., Ltd.

The bispecific T cell redirecting antibody (TRAB) is a new form of promising immunotherapy. We generated a novel TRAB, ERY974, targeting tumor-specific antigen Glypican-3 (GPC3). Using a mouse model reconstituted with human immune cells, we revealed that ERY974 is highly effective in killing various tumor types including those with non-immunogenic features. In the presentation, combination effect of ERY974 with other anti-cancer agents and its possible mechanism will also be discussed.

10:10 Networking Coffee Break

10:45 Chairperson's Remarks

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


10:50 KEYNOTE PRESENTATION: Recent Advances in Innovative Engineered Antibodies for Treatment of Cancer

William StrohlWilliam R. Strohl, PhD, Owner and President, BiStro Biotech Consulting, LLC

New technologies, including multitargeted bispecific antibodies, T cell redirecting bispecific antibodies, engagement of T cell checkpoint targets, and autologous and allogeneic forms of chimeric-antigen receptor (CAR) T and NK cells, have been employed over the past several years to improve the odds of treating cancer successfully. This presentation will explore the current clinical use of these technologies and will highlight promising new advances that offer hope for future cancer therapy.

11:20 KEYNOTE PRESENTATION: Identifying Mechanisms of Resistance to Antibody-Targeted Cancer Immunotherapy

Louis WeinerLouis Weiner, MD, Professor, Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center

We developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immunocompetent and immunodeficient mice to select for tumor cell-based genes that regulate in vivo sensitivity to immune attack. Utilizing this approach in a syngeneic Triple-Negative Breast Cancer (TNBC) model, we identified 709 genes that selectively regulated adaptive anti-tumor immunity, and validated the mechanisms that underlie the immune-related effects of expression of these genes in different TNBC lines, as well as tandem synergistic interactions. This approach has utility in identifying unknown tumor-specific regulators of immune recognition in multiple settings to reveal novel targets for future immunotherapies.

11:50 Targeting Netrin-1: From Modulating Cancer Plasticity to Strengthening Immunotherapy

Patrick MehlenPatrick Mehlen, PhD, CEO Netris Pharma, Centre Leon Berard

Netrin-1, a secreted cue, has been shown to be up-regulated in a large fraction of human cancers and has been show to promote tumor progression. An anti-netrin-1 mAb called NP137 has been preclinically developed and is currently assessed in a first-in-man-first-in-class Phase I clinical trial. The NP137 shows preclinical efficacy related to a specific effect on cancer plasticity, and preclinical data support the importance of combining NP137 with immune-checkpoint inhibitors. We will present preclinical and preliminary clinical data.

 

12:20 pm Presentation to be Announced

12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:50 Session Break

2:20 Problem-Solving Breakout Discussions

3:20 Networking Refreshment Break


PLENARY KEYNOTE SESSION

4:00 Chairperson's Remarks

4:10 Challenges and Opportunities in Engineering Protein Biopharmaceuticals

K. Dane Wittrup, PhD, C.P. Dubbs Professor, Chemical Engineering and Biological Engineering; Associate Director, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT)

Arthur C. Clarke's First Law posits that "When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong." Bearing this in mind, in this talk, I will highlight areas of protein drug development that appear poised for breakthroughs in the coming decade or so.

4:55 The Next Generation of Cancer Immunotherapy: Targeting Myeloid Immune Checkpoints

Kipp Weiskopf, MD, PhD, Resident Physician, Internal Medicine, Brigham and Women's Hospital

Immune cells of the myeloid lineage hold tremendous potential as effectors of cancer immunotherapy. The CD47/SIRPα axis is a key molecular pathway that governs the interaction between myeloid cells and tumors. Therapies that target the interaction are effective across multiple preclinical models of cancer and are now under investigation in clinical trials. Further studies have revealed additional regulators of myeloid cell activation that can be exploited as myeloid immune checkpoints.

5:40 Welcome Reception in the Exhibit Hall with Poster Viewing

7:15 End of Day

TUESDAY, MAY 1

8:00 am Registration and Morning Coffee

B7-H3, An Attractive Target For Antibody-Based Strategies: Comparing Different Approaches

8:25 Chairperson's Remarks

Soldano FerroneSoldano Ferrone, MD, PhD, Surgical Oncology, Surgery, Massachusetts General Hospital


8:30 CAR T Cells Targeting B7-H3

Gianpietro DottiGianpietro Dotti, MD, Lineberger Comprehensive Cancer Center Member, Professor, Microbiology and Immunology; Director, Lineberger Immunotherapy Program, University of North Carolina School of Medicine

The field of chimeric antigen receptors (CARs) in hematologic malignancies has been largely dominated by the adoptive transfer of T cells expressing the CD19-specific CAR for therapy of acute lymphoid leukemia and non-Hodgkin's lymphomas. We generated CAR Ts targeting the B7-H3 antigen that is expressed by many solid tumors. B7-H3.CAR Ts effectively eliminate several solid tumor cells in vitro, in PDAC orthotopic and metastatic xenograft NSG mouse models, and patient-derived xenograft (PDX) orthotopic NSG mouse models. B-H3.CAR Ts recognize the murine B7-H3, but we did not observe any decrease in hematopoietic cell numbers in blood, spleen or bone marrow, or significant tissue damage, which further encourage the clinical translation.

9:00 Targeting B7-H3 with Multiple Approaches

Ezio BonviniEzio Bonvini, MD, Senior Vice President, Research & CSO, MacroGenics, Inc.

B7-H3 is a member of the B7-family of immune regulators. While its immunological role remains unknown, B7-H3 expression is a negative prognostic factor in cancer and, owing to its limited expression in normal tissues, a suitable tumor target for exploitation by a variety of mechanistic interventions.

9:30 B7-H3 is a Potential Antibody Drug Conjugate Target for the Treatment of Solid Tumours

Kelli RyanKelli Ryan, PhD, Senior Scientist, Oncology Department, MedImmune

B7H3 is a member of the B7 family of TCR modulatory proteins that is also significantly expressed on the surface of tumor cells and the tumor vasculature, and can be a poor prognostic marker for certain cancers. This presentation will summarize the preclinical data generated upon evaluating ADCs targeting B7H3 with either tubulysin or PBD payloads.

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

EXPLOITING AND POTENTIATING KNOWN TARGETS WITH SECOND GENERATION ANTIBODIES

Chairperson's Remarks

Horacio NastriHoracio G. Nastri, PhD, Senior Director, Antibody Biotherapeutics, Incyte Corporation


10:50 Overcoming Resistance to HER2-Targeted Therapy with a Novel HER2/CD3 Bispecific Antibody

Nai-Kong V. CheungNai-Kong V. Cheung, MD, PhD, Enid A. Haupt Endowed Chair, Pediatric Oncology; Member and Attending, Pediatrics; Director, Neuroblastoma Program; Head, Robert Steel Laboratory, Memorial Sloan Kettering Cancer Center

HER2 is an established tumor target for breast, ovarian and gastric cancers. We explored a novel HER2/CD3 bispecific antibody (HER2-BsAb) platform which, in addition to preserving the anti-proliferative effects of trastuzumab, recruits and activates circulating T cells, promoting T cell tumor infiltration, as well as ablating HER2(+) tumors resistant to standard HER2-targeted therapies. HER2-BsAb-mediated cytotoxicity is relatively insensitive to PD-1/PD-L1 immune checkpoint inhibition, although the addition of ICI does improve its efficacy.

11:20 Unbiased Functional Screening of Large Bispecific Antibody Panels to Unlock Novel Biology

Mark ThrosbyMark Throsby, PhD, CSO, Merus NV

The bispecific antibody format represents an emerging therapeutic modality. We have developed a set of robust and validated technologies that permits unbiased in-format functional screening to identify human full-length IgG bispecific antibodies candidates with superior therapeutic properties. Two case studies will be presented where this approach has been successfully employed to discover lead candidates with differentiating properties that are now in clinical development.

11:50 Balancing Selectivity and Efficacy of Bispecific EGFR x c-MET Antibodies and Antibody-Drug Conjugates

Achim Doerner, PhD, Principal Scientist, Protein Engineering and Antibody Technologies, Merck KGaA Darmstadt, Germany

Therapies targeting EGFR often suffer from toxicities due to basal EGFR expression in normal tissue and may face limited efficacy through c-MET activation. Hence, we aim to construct bispecific EGFR x c-MET antibodies employing affinity-optimized binding moieties to balance both high selectivity and anti-tumor efficacy and to evaluate their potential for an innovative antibody-drug conjugate approach.

Ligand_Pharma12:20 pm Luncheon Presentation I to be Announced


12:50 Luncheon Presentation II (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing

2:00 KEYNOTE PRESENTATION: Combining Local Immunotoxins Targeting Mesothelin with CTLA-4 Blockade Synergistically Eradicates Murine Cancer by Promoting Anti-Cancer Immunity

Ira PastanIra H. Pastan, MD, Scientist, NIH NCI

Immune check point blockade benefits a limited number of patients. SS1P and LMB-100 are immunotoxins used to treat mesothelin expressing cancers. To investigate synergy between check point inhibitors and immunotoxins, we developed a Balb/C mouse model using mouse breast cancer cells expressing human mesothelin. When immunotoxin was injected into the tumors and anti-CTLA-4 given I.P., anti-tumor immunity developed resulting in complete regressions of injected and distal un-injected tumors.

OVERCOMING MECHANISMS OF RESISTANCE TO IMMUNOTHERAPY FOR CHECKPOINT INHIBITORS

2:30 Chairperson's Remarks

Paul B. Chapman, MD, Physician & Scientist, Memorial Sloan Kettering Cancer Center

2:35 Loss of Peptide Presentation Apparatus as a Mechanism of Resistance to Checkpoint Inhibitor Therapy

Paul ChapmanPaul B. Chapman, MD, Melanoma Clinical Director, Attending Physician, Memorial Sloan Kettering Cancer Center; Professor, Medicine, Weill Cornell Medical College

Since melanoma cells frequently lose expression of HLA alleles, a potentially common mechanism of resistance to checkpoint inhibitors would be loss of antigen processing and presentation machinery. We are evaluating pre- and post-treatment tumor biopsies for defects in HLA class I antigen processing machinery as a mechanism for resistance to checkpoint inhibitors.

3:05 Antibody Protein Sequencing with Mass Spectrometry

 

Mingjie Xie, CEO, Rapid Novor, Inc.

Many applications in antibody engineering require the direct sequencing of antibody proteins. At Rapid Novor (rapidnovor.com), we have developed a robust workflow and routinely sequenced antibody proteins. Here we share the success experiences, examine common mistakes novices make, and present our practices to ensure the correctness of every amino acid.

3:20 Sponsored Presentation (Opportunity Available)  

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:25 Understanding Responses to Cancer Therapy: The Tissue is The Issue, but the Scoop is in the Poop

Jennifer Wargo, MD, Melanoma Research, MD Anderson Cancer Center

We have made major advances in cancer therapy through the use of targeted therapy and immunotherapy, however responses are not universal and are not always durable. A better understanding of mechanisms of response and resistance have been elucidated via analysis of longitudinal tumor and blood samples on therapy - providing potentially actionable strategies to overcome resistance. In addition to this, there is a growing appreciation of the role of the gut microbiome in modulating systemic and anti-tumor immune responses and insights into the role of the gut microbiome in response to immune checkpoint blockade will be discussed.

4:55 Personalized Cancer Vaccines as a Strategy to Overcome Resistance to Immunotherapy

Patrick OttPatrick Ott, MD, PhD, Clinical Director, Melanoma Center; Clinical Director, Center for Immuno-Oncology, Dana-Farber Cancer Institute; Assistant Professor of Medicine, Harvard Medical School

Clonal evolution of cancer cells can lead to immune evasion, enabling tumors to avoid the attack by the immune response. Neoantigens, which arise from somatic tumor mutations, are highly immunogenic and therefore key targets of tumor cytolysis in vivo. Personalized cancer vaccines, by targeting a spectrum of different neoantigens expressed by a patient's tumor rather than a single antigen, can directly address the therapeutic challenge of tumor clonal heterogeneity and therefore potentially overcome resistance to immunotherapy.

5:25 End of Antibodies for Cancer Therapy

5:30 Registration for Dinner Short Courses*

*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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