Targeting Tumor Myeloid Cells


Cambridge Healthtech Institute 第1届
肿瘤骨髓细胞标靶
肿瘤内微环境 (TME) 的再型塑

第15届Discovery on Target其中一环

本会议以骨髓肿瘤细胞标靶化为主题,癌症免疫研究及癌症免疫疗法相关研究人员、技术提供商主管将齐聚一堂,讨论快速崛起的该领域目前课题及机会。

Final Agenda


RECOMMENDED ALL ACCESS PACKAGE:

· September 25 Symposium: Immunomodulatory Small Molecules

· September 25 Short Course: Immunology Basics for Chemists

· September 26-27 Conference: NK Cell-Based Cancer Immunotherapy

· September 27-28 Conference: Targeting Tumor Myeloid Cells

· September 27 Short Course: Impact of Convergence of Immunotherapy and Epigenetics on Drug Discovery

· September 28-29 Symposium: Tackling Rare Diseases


Wednesday, September 27

11:50 am Conference Registration Open

12:20 pm Plenary Keynote Program

(click here for details)

2:00 Refreshment Break in the Exhibit Hall with Poster Viewing

TUMOR-ASSOCIATED MACROPHAGES (TAMs) AS THERAPEUTIC TARGETS

2:45 Welcome Remarks

Kip Harry, Senior Conference Director, Cambridge Healthtech Institute

2:50 Chairperson's Opening Remarks

Bob Uger, Ph.D., CSO, Trillium Therapeutics, Inc.

2:55 KEYNOTE PRESENTATION: Tumor-Associated Macrophages as a Therapeutic Target

Alberto Mantovani, M.D., Professor, Pathology, Humanitas University; Scientific Director, Istituto Clinico Humanitas

Macrophages are key orchestrators of chronic inflammation. They respond to microenvironmental signals with polarized genetic and functional programmes. M1 and M2 cells represent simplified extremes in a universe of functional states. Available information suggests that some TAM are an M2 population. Polarization of phagocytes sets these cells in a tissue remodeling and repair mode and orchestrate the smoldering and polarized chronic inflammation associated to established neoplasia. Intrinsic metabolic features and orchestration of metabolism are key components of macrophage polarization and function. Recent studies have begun to address the central issue of the relationship between genetic events causing cancer and activation of protumor, smoldering, non-resolving tumor-promoting inflammation. New vistas have emerged on molecules associated with M2 or M2-like polarization and its orchestration in cancer. Recently, proof-of-principle has been obtained that targeting TAM can be beneficial in human cancer. Moreover, complement has emerged as a key component of tumor-promoting inflammation. Classic and novel therapeutic targets will be discussed.

3:25 Macrophage-Targeted Cancer Immunotherapy

Carola Ries, Ph.D., Head, Cancer Immunotherapy I, Pharma Research and Early Development (pRED), Roche Innovation Center Munich

To therapeutically target TAMs, we harnessed their dependence on the key survival factor, macrophage colony-stimulating factor 1 (CSF1), and developed a monoclonal antibody (Emactuzumab/RG7155) that blocks dimerization and activation of human CSF1R. Treatment of cancer patients with Emactuzumab substantially reduces the intratumoral TAM infiltrate. We will present data on a cancer immunotherapy combination, which targets TAMs and stimulates an anti-tumoral T cell response leading to tumor remission in preclinical mouse models.

3:55 Sponsored Presentation (Opportunity Available)

4:25 Refreshment Break in the Exhibit Hall with Poster Viewing

TUMOR-ASSOCIATED MACROPHAGES (TAMs) AS THERAPEUTIC TARGETS (Cont.)

5:00 Modulation of the Tumor Microenvironment by Large and Small Molecules: A Lesson from the Anti-PD-1 and CFS-1R Inhibitor Combination

Daniela Cipolletta, Ph.D., Lab Head, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research (NIBR)

We have used murine models to monitor the immune response upon perturbation of the tumor microenvironment with large and small molecules. This approach has enabled our understanding of tumor-induced immune modulation and the identification of novel combinatorial strategies in specific cancer settings.

5:30 Discovery and Development of DCC-3014, a Highly Specific Inhibitor of CSF1R Kinase

Daniel L. Flynn, Ph.D., CSO and Founder, Deciphera Pharmaceuticals

The discovery and development of DCC-3014 will be presented, including the use of Deciphera's switch control platform to identify highly specific inhibitors of CSF1R kinase. DCC-3014 potently inhibits CSF1R, while sparing near neighbor kinases FLT3, KIT, and PDGFRs by >100 to >1,000 fold, and additionally sparing a 300 kinase panel by >1,000 fold. Cellular studies, in vivo PK/PD studies, and in vivo efficacy studies in syngeneic cancer models (single agent and in combination with anti-PD1) will also be presented.

6:00 Class IIa HDAC Inhibition Promotes an Anti-Tumor Macrophage Phenotype that Induces Breast Tumor Regression and Inhibits Metastasis

Jennifer Guerriero, Ph.D., Instructor of Medicine, Lead Scientist of the Immuno-Oncology Group, Letai Laboratory, Dana-Farber Cancer Institute

We recently reported that a first-in-class selective class IIa HDAC inhibitor (TMP195) influenced human monocyte responses to colony stimulating factors CSF-1 and CSF-2 in vitro. Here, we utilize a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumor microenvironment and reduces tumor burden and pulmonary metastases through macrophage modulation. TMP195 induces recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumors.

6:30 Close of Day

6:30 Dinner Short Course Registration

Click here for details on short courses offered.

Thursday, September 28

7:30 am Registration Open

8:00 Interactive Breakout Discussion Groups with Continental Breakfast

Grab a cup of coffee and join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Details on the topics and moderators are available on the conference website.

TARGETING THE CD47-SIRPa BLOCKADE

9:00 Chairperson's Remarks

Michael M. Goldberg, M.D., President and CEO, Navidea Biopharmaceuticals, Inc. & Macrophage Therapeutics, Inc.

9:05 A Portfolio of Humanized Anti-CD47 Monoclonal Antibodies with Diverse Combinations of Functional Properties and Preclinical Anti-Tumor Activity

Robert W. Karr, M.D., CSO, Tioma Therapeutics

Anti-CD47 antibodies have also been shown to promote an anti-tumor adaptive immune response. Ti-061, Tioma's first generation humanized anti-CD47 antibody, has preclinical anti-tumor activity in vitro and in vivo and is being studied in a Phase I trial. Tioma's second generation anti-CD47 antibodies have novel combinations of functional properties, including direct killing of tumor cells, minimal RBC binding and increasing phagocytosis of tumor cells, potentially enhancing their anti-tumor activity.

9:35 TTI-621 (SIRPαFc): A Checkpoint Inhibitor of the Innate Immune System that Blocks the CD47 "Do Not Eat" Signal

Bob Uger, Ph.D., CSO, Trillium Therapeutics, Inc.

Trillium Therapeutics is developing TTI-621 (SIRPαFc), a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG1. It is designed to block the CD47 "do not eat" signal and engage activating Fc receptors on macrophages to enhance phagocytosis and anti-tumor activity and is currently being evaluated in two Phase I clinical studies. This presentation will discuss the preclinical rationale and emerging clinical data for this novel innate immune system checkpoint inhibitor.

10:05 Selective Targeting of SIRP Alpha Induces Potent Memory Anti-Tumor Immune Responses in Mice and Does Not Prevent SIRP Gamma Dependent Human T Cell Responses

Bernard Vanhove, Ph.D., COO, OSE Immunotherapeutics

Using murine models of TNBC and HCC, we noticed a preclinical efficacy of antagonistic anti-SIRPalpha mAbs in monotherapy or in combination with anti-PDL-1 and 4-1BB mAbs. Combinations elicited anti-tumor T cell responses. In humans, but not in mice, CD47 also interacts with SIRPgamma expressed by T cells, playing a role in human T cell proliferation. We show here that blocking CD47/SIRPgamma interaction is deleterious for T cell responses in vitro while specifically targeting SIRPalpha is "T cell friendly".

10:35 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

11:20 Targeting CD47 with High-Affinity SIRPα Fusion Protein to Enhance Both Innate and Adaptive Immunity against Cancer without Hematological Toxicity

Hong I. Wan, Ph.D., Vice President, Early Development and Translational Medicine, Alexo Therapeutics

CD47 is a widely expressed cell surface protein that functions as a marker of self. Interaction of CD47 with signal regulatory protein-α (SIRPα), its receptor on macrophages, inhibits phagocytosis. CD47 blockade may enhance both innate and adaptive immunity against cancer and is being evaluated as a new immunotherapy. Fusion proteins comprised of the N-terminal D1 domain of SIRPα and inactive Fc domains were engineered to bind CD47 with high affinity and prevent interaction of CD47 with wild type SIRPα. These high-affinity SIRPα fusion proteins enhanced the activity of multiple anti-cancer antibodies and have minimal effect on normal blood cells both in vitro and in vivo. ALX148, a high-affinity CD47 blocker designed to avoid toxicity on CD47-expressing blood cells, is currently in clinical development in a broad spectrum of malignancies (NCT03013218).

11:50 Targeting the Tumor Microenvironment by Selectively Depleting the Tumor Supporting M2 Macrophages

Michael M. Goldberg, M.D., President and CEO, Navidea Biopharmaceuticals, Inc. & Macrophage Therapeutics, Inc.

Macrophage Therapeutics has developed a highly targeted agent that can deliver therapeutic payloads with extremely high Kds, on the order of 10-11 or higher, targeted to the mannose receptor (CD206). The mannose receptor is only expressed on activated macrophages and internalizes and recycles every 15 minutes. MT1002 targets CD206 and delivers a therapeutic agent linked to the targeted dextran backbone with a pH sensitive linker. Data will be presented that demonstrates that MT1002 depletes the TAMs via apoptosis, without any effect on non-activated macrophages.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:50 Refreshment Break in the Exhibit Hall with Poster Viewing

NOVEL AGENTS TARGETING TUMOR-ASSOCIATED MYELOID CELLS

2:35 Chairperson's Remarks

Bernard Vanhove, Ph.D., COO, OSE Immunotherapeutics

2:40 Overcoming Resistance to Checkpoint Blockade by Selectively Targeting PI3K-Gamma in Tumor Myeloid Cells

Jeffery Kutok, M.D., Ph.D., CSO, Biology and Translational Medicine, Infinity Pharmaceuticals

IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma which is highly expressed in tumor associated myeloid cells. In preclinical studies, IPI-549 increases anti-tumor immunity by reprogramming tumor-associated myeloid cells from the M2, pro-tumor phenotype to the M1, anti-tumor phenotype and activating anti-tumor T cell responses. IPI-549 also overcomes immune checkpoint blockade resistance in preclinical tumor models.

3:10 EP4 Antagonism in Combination Immuno-Oncology Therapeutic Approaches

Xingfeng Bao, Ph.D., Head, Immuno-Oncology, Integrated Biology Engine, Eisai AiM Institute, Eisai, Inc.

PGE2 in the tumor microenvironment contributes to the accumulation of immunosuppressive myeloid cells by interacting with the EP4 receptor on newly arriving monocytes, skewing their development into MDSCs and TAMs. The EP4 antagonist E7046, now in Phase I/Ib trials, inhibits this interaction and enhances formation of a more favorable anti-tumor immune milieu. This approach combines well preclinically with T cell-directed immunotherapies such as checkpoint inhibitors in boosting anti-tumor immunity.

3:40 Session Break

3:55 Imprime PGG - A Yeast-Derived Pathogen-Associated Molecular Pattern (PAMP) Triggers the Anti-Cancer Immunity Cycle to Potentiate the Efficacy of Immune Checkpoint Inhibitors

Jeremy R. Graff, Ph.D., CSO and Senior Vice President, Research, Biothera Pharmaceuticals, Inc.

Imprime has been safely administered to >400 human subjects. Imprime triggers a cascade of immune activating events that re-polarize the immunosuppressive tumor microenvironment and elicit maturation of antigen presenting cells. Unlike other PAMPs (TLR and STING agonists), Imprime is administered systemically. In preclinical tumor models, Imprime robustly enhances the anti-tumor efficacy of CPIs. Accordingly, Imprime is now being explored in multiple Phase II clinical trials in combination with pembrolizumab.

4:25 Effective Combinatorial Immunotherapy for Castration-Resistant Prostate Cancer

Xin Lu, Ph.D., John M. and Mary Jo Boler Assistant Professor, Department of Biological Sciences, Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame

Targeted therapy against myeloid-derived suppressor cells (MDSCs), using multikinase inhibitors such as cabozantinib and BEZ235, also showed minimal anti-tumor activities. Strikingly, primary and metastatic CRPC showed robust responses to the synergistic effect when ICB was combined with MDSC-targeted therapy. Mechanistically, the combination efficacy was due to the upregulation of IL-1RA and suppression of MDSC-promoting cytokines secreted by mCRPC cells.

4:55 Close of Conference

* 活动内容有可能不事先告知作更动及调整。

Choose your language
Chinese
Japanese
Korean
English

Catalog

Celebrating 25 Years

Submit A Poster

View All Sponsors

View Media Partners



免费电子邮件通知服务