Peptides in Cancer Therapy

The unique properties of peptides, namely their specificity, small size, low levels of toxicity, ease of synthesis and modification, are driving an increasing interest in peptides as an effective treatment of cancer, particularly in immuno-oncology.

Cambridge Healthtech Institute’s Peptides in Cancer Therapy symposium provides a unique opportunity to discuss the latest developments in peptide-based cancer therapy with dedicated sessions on peptide cancer vaccines, immunotherapies and conjugates. Attention will also be paid to inducing immune responses, improving delivery and minimizing toxic side effects, supported by the latest scientific findings and company updates.

Final Agenda

Wednesday, March 29

7:45 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

Peptide-Based Vaccines in Oncology

8:25 Chairperson’s Opening Remarks

Jesse Dong, Ph.D., Vice President, Peptide Chemistry, Neon Therapeutics

8:30 FEATURED PRESENTATION: Advantages of a Peptide-Based Vaccine Designed to Activate CD4+ T Cells in Cancer Immunotherapy

Eric_von_HofeEric von Hofe, Ph.D., President, Antigen Express

The low toxicity and high specificity of peptides make them attractive as drug development candidates for a variety of applications, including cancer vaccines. We have developed a modified HER2 peptide cancer vaccine that specifically activates both CD4+ and CD8+ T cells. In addition to long-lasting and specific CD4+ and CD8+ T cell responses, encouraging efficacy data in breast cancer patients has been observed in a controlled, randomized Phase II study.

9:00 Epitope-Enhanced Peptide Vaccine for Prostate Cancer: Translation from Mice to Human Clinical Trials

Jay_BerzofskyJay A. Berzofsky, M.D., Ph.D., Branch Chief, Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH

We developed an epitope-enhanced-peptide prostate cancer vaccine using epitopes from TARP antigen. Epitope enhancement increased affinity for HLA-A2.1. Peptides induced CD8 T cell responses in HLA-transgenic mice and human T cells that killed human tumor cells. In a Phase I trial in stage D0 prostate cancer with rising PSA after tumor resection, 74% of vaccinated patients at one year had a decreased PSA slope (p=0.0004). A Phase II trial is underway.

9:30 Development Strategies of Neo-Antigen-Based Personalized Cancer Vaccines

Jesse_DongJesse Dong, Ph.D., Vice President, Peptide Chemistry, Neon Therapeutics

Neoantigens arise as a result of somatic mutations during the development and progression of tumors. They are inherently non-self and are seen as foreign by the immune system. Mounting evidence suggests that immune rejection of tumours, for example which is seen with checkpoint inhibitors, may be mediated by recognition of neoantigens. Neon’s personalized cancer vaccine targets neoantigens unlocking the immune system to attack tumors.

10:00 Networking Coffee Break

Peptide-Based Vaccines in Oncology

10:30 Paradigm Shift in Oncology: Translating B Cell Epitope Peptide-Based Cancer Vaccines to the Clinic and Future Combination Immunotherapies

Pravin_KaumayaPravin T.P. Kaumaya, Ph.D., Professor, Division of Vaccine Development/Peptide & Protein Engineering Laboratory, Ohio State University

We have created and established a portfolio of validated peptide epitopes against multiple receptor tyrosine kinases and we have identified the most biologically effective combinations of EGFR (HER-1), HER-2, HER-3, VEGF and IGF-1R peptide vaccines/mimics to selectively inhibit multiple receptors and signaling pathways. This presentation will detail our ongoing studies based on the development of combinatorial immunotherapeutic strategies that act synergistically to enhance immune-mediated tumor killing aimed at addressing mechanisms of tumor resistance for several tumor types.

11:00 Inducing Immune Responses to Tumor-Associated Carbohydrate Antigens by a Carbohydrate Mimetic Peptide Vaccine: Clinical Experience in Phase I and Phase II Trials in Breast Cancer Patients

Thomas_Kieber-EmmonsThomas Kieber-Emmons, Ph.D., Professor, Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences

We have developed a first-in-man peptide based vaccine that induces antibodies cross-reactive with Tumor Associated Carbohydrate Antigens (TACA). This peptide is a computer engineered pan mimic of TACAs. Immunization with this vaccine was found to be safe and tolerable in Phase I and II clinical trials, and induces functional antibodies that display a cell-death mediated therapeutic benefit. The data suggest that the vaccine-induced anti-tumor immune response in combination with standard of care chemotherapy may further improve clinical outcome.

11:30 Vaccines for the Prevention of Breast Cancer

Keith_KnutsonKeith L. Knutson, Ph.D., Professor, Immunology, Director, Mayo Clinic Florida Cancer Research Program, Mayo Clinic Center for Immunology and Immune Therapies

Breast cancer causes 500,000 deaths each year. Rather than continue to add to the costs of treatment, we should advance promising approaches for prevention such as vaccination. One approach for a breast cancer vaccine is to target aberrantly expressed ‘self’ antigens. To produce such a vaccine, we’re aiming to achieve key milestones, namely identifying peptide epitopes from cancer antigens and identifying systems that induce durable T cell responses.

12:00 pm Sponsored Presentation (Opportunity Available)  

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

Peptide-Drug Conjugates

1:25 Chairperson’s Remarks

Pravin T.P. Kaumaya, Ph.D., Professor, Division of Vaccine Development/Peptide & Protein Engineering Laboratory, Ohio State University

1:30 Synthesis, Purification and Formulation of a New T Cell Vaccine Using 5 Novel Proteins

John_BonfiglioJohn N. Bonfiglio, Ph.D, MBA, President and COO, TapImmune

TPIV 200 is a T cell vaccine targeting Folate Receptor Alpha-a receptor overexpressed in ovarian, triple negative breast and non-small cell lung cancers. After initial positive results in an investigator-sponsored Phase I study, it was essential to develop a stable, soluble formulation that could be used for Phase II and beyond. The work included solving some difficult purification problems and formulating the product to be compatible with other additives such as adjuvants.

2:00 Evaluating Multivalent Peptidomimetic Conjugates as Therapeutics for Castration-Resistant Prostate Cancer

Kent_KirshenbaumKent Kirshenbaum, Ph.D., Professor, Chemistry, NYC Chemistry

There is an urgent need for new strategies to block androgen receptor (AR) function in prostate cancer. We describe sequence-specific peptoid oligomers as scaffolds for constructing precise multivalent displays of AR ligands. The peptoid conjugates suppress proliferation of multiple AR-expressing prostate cancer cell lines including those that are resistant to enzalutamide and ARN509. The conjugates display attractive pharmacological characteristics and deter tumor growth in mouse xenograft models of prostate cancer.

2:30 Development of BT1718, a Bicycle Peptide-Drug Conjugate (BDC) Targeting MT1-MMP for the Treatment of Solid Tumors

Peter Park, VP, Oncology R&D, Bicycle Therapeutics

MT1-MMP (MT1) is a cell surface membrane protease normally involved in tissue remodeling and overexpression of MT1 has been linked to cancer invasiveness and poor prognosis in many solid tumors. BT1718 is a Bicycle drug conjugate (BDC) containing the optimized MT1-binding peptide covalently linked through a hindered disulfide linker to the potent anti-tubulin agent DM1. BT1718 shows potent antitumor activity in human solid tumor xenograft models in mice, including models of fibrosarcoma, lung and breast cancer, at doses that are well tolerated, demonstrating the therapeutic potential of this small molecule targeting approach for the treatment of cancer.

3:00 Networking Refreshment Break

Peptides-Drug Conjugates and Targeting MCL-1


3:15 Hydrocarbon Stapled Peptide Antagonists as Novel Agents for Targeting MCL-1

Rahele_Rezaei-AraghiRaheleh Rezaei-Araghi, Ph.D., Postdoctoral Associate, Biology Department, MIT

Mcl-1 has emerged as a widely expressed pathologic factor in human cancer. Previous studies indicate that hydrocarbon stapling can confer improved affinity for Mcl-1. The virtually unlimited structural variations within this design scheme present a challenge. To address this problem, we applied synthetic libraries, which enable the construction and screening of chemically modified repertoires of peptidic scaffolds. By applying this method, molecules with high affinity and selectivity were identified.

3:45 Close of Symposium