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Immunomodulatory Therapeutic Antibodies for Cancer Conference - Day 2

2013 Archived Content

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Emerging Targets 

8:25 am Chairperson's Opening Remarks

Lawrence J. Thomas, Ph.D., DABT, CMAR, Senior Director, Preclinical Research and Development, Celldex Therapeutics, Inc. 

8:30 Immunocytokines: A Novel Potent Class of Armed Antibodies

Catherine HutchinsonCatherine Hutchinson, Ph.D., Research Scientist, Philochem, Switzerland

The severe toxicity of recombinant cytokines even at low doses limits their therapeutic potential, but this can be mitigated by using monoclonal antibodies to target their delivery. This talk will cover the latest advanced preclinical and clinical data of the Philogen group, detailing the discovery and development of armed antibodies against angiogenesis-specific markers, which are attractive targets relevant to many angioproliferative diseases.

9:00 Mechanism of Action and Progress Update for MGA271: An Fc-Enhanced mAb Targeting B7-H3 in Solid Tumors

Ezio Bonvini, M.D., Senior Vice President, Research, MacroGenics, Inc.

Characterization of murine monoclonal antibodies generated from cancer cell and/or stem cell-based immunizations identified a panel targeting the immunoregulatory protein B7-H3 displaying broad tumor reactivity but limited binding to normal tissue. Preclinical evaluation of MGA271, an Fc-enhanced anti-B7H3 mAb, revealed strong ADCC activity against a broad range of tumor cell types, potent antitumor activity in xenograft models employing human FcR transgenic mice and a favorable safety profile in non-human primate toxicology studies. A phase I/IIa clinical study of MGA271 in patients with B7-H3-positive metastatic or recurrent adenocarcinoma is currently recruiting patients.

9:30 Preclinical Update: Development of a Human Anti-CD27 Monoclonal Antibody as a Potential Cancer Therapy

Lawrence J. ThomasLawrence J. Thomas, Ph.D., DABT, CMAR, Senior Director, Preclinical Research and Development, Celldex Therapeutics, Inc.

Agonist antibodies binding the co-stimulatory molecule CD27 have potent antitumor activity in murine tumor models through boosting of durable T cell antitumor immunity. Anti-CD27 antibodies have also been shown to mediate the direct killing of CD27-expressing tumors. Such preclinical data supports the therapeutic potential of this anti-CD27 monoclonal antibody as a cancer immunotherapy.

10:00 Sponsored Presentation (Opportunity Available)

10:15 Refreshment Break in the Exhibit Hall with Poster Viewing

11:00 Targeting CD47-SIRPα Interactions for Potentiating Antibody Therapy in Cancer

Hanke Matlung, Ph.D., Postdoctoral Fellow, Blood Cell Research, Sanquin Blood Supply Foundation, The Netherlands 

We will present findings demonstrating that interactions between CD47 expressed on cancer cells and the myeloid inhibitory immunoreceptor SIRPα form a barrier for the antibody-mediated destruction of cancer cells. These findings identify the CD47-SIRPα interaction as a potential generic target for improving the efficacy of cancer antibody therapeutics.

11:30 Proteomic Identification of Cancer Targets for the Development of Two Novel Antibody Therapeutics

Thi-Sau Migone, Ph.D. Chief Scientific Officer, Igenica

This talk will focus on two first in class targets discovered at Igenica, currently in preclinical development. We will cover target selection, preclinical efficacy and safety data, in addition to assessment of antibody drug conjugates. Some of the challenges and opportunities encountered while developing novel antibody therapeutics for the treatment of cancer will be discussed. 

WorldCare Clinical LLC12:00 Image Assessment in Immunotherapeutic Trials: Combining irRC and RECIST 1.1

Patrick Chokron, Director, Software Engineering, WorldCare Clinical

Current methods for assessing tumor burden (RECIST) assume that early increases in tumor growth or new lesions signal disease progression.  This is not the case with immunomodulatory therapies.  We will highlight the advantages of performing a combination assessment using both RECIST 1.1 and the newer immune-related response criteria (irRC).

12:30 Luncheon Presentation (Opportunity Available) or Lunch on Your Own


Clinical Development of Immunomodulatory Antibodies 

1:55 Chairperson's Opening Remarks

Lex Bakker, Ph.D., Chief Development Officer, Merus, The Netherlands 

2:00 Clinical Trials Design for Cancer Immune Therapies

Harriet KlugerHarriet Kluger M.D., Associate Professor, Yale Cancer Center

Clinical development of immune therapies is challenging; standard drug development paradigms are often not applicable. Modifications are necessary in regard to dose escalation, management and definition of toxicities, within-patient dose reduction, and radiographic assessment of response to therapy. In later stage trials new definitions of study endpoints are needed. Correlative biomarker studies are complex, and require assessment of baseline immune function and tumor characteristics.

2:30 Characteristics and Management of Immune-Related Adverse Effects Associated with Ipilimumab, a New Immunotherapy for Metastatic Melanoma

Stephanie AndrewsStephanie Andrews, Oncology Nurse Practitioner, Moffitt Cancer Center

Immune-Related Adverse Effects are a new phenomenon related to advances in the use of the first FDA approved monoclonal antibody Ipilimumab for metastatic melanoma. These side effects are different than side effects of traditional cytotoxic regimens. These immune-mediated side effects include enterocolitis, hepatitis, dermatitis, neuropathy andendocrinopathy.

Bispecific Immunomodulatory Antibodies 

3:00 Safety Challenges to Development of Immune System Activating Antibodies

Rakesh DixitRakesh Dixit, Ph.D., DABT, Vice President, Research & Development, Global Head, Biologics Safety Assessment, Pathology & LAR, MedImmune (AstraZeneca Biologics)

Immune system activating antibodies with abilities to harness and enhance an individual patient's immune system and target tumors are revolutionizing the treatment of many deadly cancers. However, many immune-activating biologics have serious dose-limiting toxicities, including cytokine storm-associated critical toxicities and serious autoimmune diseases in multiple key organs that may limit their long-term use. Nonclinical and clinical safety challenges and risk mitigation opportunities will be discussed in the context of immune activating antibodies, including bispecific BiTE antibodies.

3:30 Refreshment Break

3:45 MCLA-117: ABiclonics – ENGAGE Bispecific IgG Product Lead Targeting CLEC12A and CD3 in AML

Lex BakkerLex Bakker, Ph.D., Chief Development Officer, Merus, The Netherlands

MCLA-117, a common light chain T cell-engaging full-length human bispecific antibody (Biclonics – ENGAGE) was discovered that targets CD3 on T cells and CLEC12A on acute myeloid leukemia (AML) blasts and leukemic stem cells. Co-incubation of resting patient T cells and AML cells with MCLA-117 results in efficient tumor cell lysis. Clinical application of MCLA-117 potentially provides a therapy in AML that more efficiently eradicates the cancer cells and prevents relapse.

4:15 Bispecific Antibody Targeting CD47 Aiming at Increasing Phagocytosis of Cancer Cells

Krzysztof MasternakKrzysztof Masternak, Ph.D., Head of Biology, Novimmune SA, Switzerland

CD47 is a ubiquitously expressed transmembrane receptor with multiple functions in cell-to-cell communication. Its interaction with SIRPα expressed in macrophages and DCs inhibits their phagocytic function. Overexpression of CD47 in cancer cells is often observed and it is believed to help cancer cells escape immune surveillance. We have generated bispecific antibodies (BsAbs) that preferentially neutralize CD47-SIRPα interaction on cancer cells.

4:45 Close of Conference

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