Recent studies have shown that the more tumor-specific mutations, or neoantigens - the cancer cells - have the greater chance that the tumor will not be tolerated by the immune system. With increasing access to next-generation sequencing (NGS) technologies, as well as mass spectrometry, cancer researchers are scouring the tumor genome and proteogenome to find new therapies. Cambridge Healthtech’s Inaugural Neoantigen-Based Immunotherapies program is proud to discuss the cutting-edge research that combines cancer, immunology and proteogenomics to design the next generation of personalized cancer immunotherapies.

Final Agenda

Thursday, March 14

7:00 am Registration Open and Morning Coffee


KEYNOTE SESSION: FOCUS ON THE FUTURE

8:25 Chairperson’s Opening Remarks

Margaux Stack-Babich, Program Manager, Immunotherapy Foundation

8:30 Clinical Applications of Neoantigen Based Immunotherapy

Ezra Cohen, MD, Associate Director, Moores Cancer Center, Professor of Medicine, UCSD

8:40 Translation of Cancer Vaccines

Karin Joos, PhD, CSO, Gritstone Oncology

8:50 Challenges to Overcome

Stephen Schoenberger, PhD, Center Head; Professor, Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology

9:30 PANEL DISCUSSION: Promise and Reality of Personalized Neoantigen Therapies

Moderator: Margaux Stack-Babich, Program Manager, Immunotherapy Foundation

Panelists: Karin Joos, PhD, CSO, Gritstone Oncology

Ezra Cohen, MD, Associate Director, Moores Cancer Center, Professor of Medicine, UCSD

Stephen Schoenberger, PhD, Center Head; Professor, Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology

  • Overall view of the field – what’s happened and what do we want to happen
  • New clinical trial data – challenges to overcome
  • Shared neoantigens versus unique neoantigens
  • Finding the most immunogenic neoantigens
  • Translation of cancer vaccines

10:00 Sponsored Presentation (Opportunity Available)

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

IDENTIFICATION METHODS AND SELECTION OF IMMUNOGENIC NEOANTIGENS

11:15 RNA Generated Frameshift Antigens in Tumors Are Useful Both in Diagnosis and Vaccination

Stephen Albert Johnston, PhD, CEO, Calviri; Director, Center for Innovations in Medicine, Professor, School of Life Sciences, Biodesign Institute, ASU

We have discovered that RNA frameshift (FS) variants formed by INDELs in microsatellites and mis-splicing of exons are a rich source of highly immunogenic neoantigens. We make arrays containing all of these possible (400K) FS peptides. Antibody reactivity to the FS peptides can be measured from a drop of blood. The arrays are remarkable in cancer diagnosis and make generation of cancer vaccines simple.

11:45 Personalized Cancer Vaccine Trials at Mount Sinai and Ongoing Research in Neoantigen Identification

Alex Rubinsteyn, PhD, Instructor, Genetic and Genomic Sciences, Icahn School of Medicine at Mount Sinai

This talk will present intermediate results from three ongoing personalized cancer vaccine trials at Mount Sinai Hospital. All three trials use the same underlying computational methodology for neoantigen identification and deliver selected peptides in combination with Poly-ICLC. There will also be discussion of new methodology for T-cell epitope prediction and under-explored sources of neoantigens, such as splicing abnormalities and gene fusions.

12:15 pm Sponsored Presentation (Opportunity Available)

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break

IDENTIFICATION AND SELECTION OF IMMUNOGENIC NEOANTIGENS (CONT.)

1:55 Chairperson’s Remarks

Alex Rubinsteyn, PhD, Instructor, Genetic and Genomic Sciences, Icahn School of Medicine at Mount Sinai

2:00 ATLAS™ – Finding True Neoantigens for Cancer Vaccines

Pamela Carroll, PhD, Senior Vice President, Immuno-oncology, Genocea Biosciences

Genocea is applying its proprietary technology platform ATLAS to identify clinically relevant T cell antigens based on patients’ own immune responses to their cancers. Its first neoantigen vaccine, GEN-009, is currently being evaluated in Phase 1/2a clinical trials. ATLAS differs from in silico neoantigen discovery methods as an HLA agnostic assay that identifies both CD4+ and CD8+ T cell neoantigens, and uniquely distinguishes between mutations that elicit stimulatory versus inhibitory T cell responses.

2:20 Neoantigen Prediction from Chromoplexy

George Vasmatzis, PhD, Director, Biomarker Discovery Program, Center for Individualized Medicine, Mayo Clinic

Chromoplexy is present in many tumors and could result in the transcription of truncated genes and many potential neoantigens. To predict such neoantigens, integration of MPseq and RNAseq was applied on malignant pleural mesothelioma, a disease often associated with complex structural chromosomal abnormalities. MHC typing was performed using RNAseq, while NetMHC and NetMHCpan were used to predict the neoentigen binding affinity. Our results may have implications in emergent neoantigen-related immunotherapies.

2:40 How to Find a Neoantigen in silico: Insights from the Tumor Neoantigen Selection Alliance

Nadine Defranoux, PhD, Program Manager, Parker Institute for Cancer Immunotherapy

It is now accepted the mutation-derived neoantigens can elicit an anti-tumor immune response and may potentially drive a substantial part of it. Identifying neoantigens accurately from the exome sequence of a tumor could have immense therapeutic benefit but remains a steep challenge. Here I will discuss our efforts at the Parker Institute to understand i) what makes a neoantigen immunogenic and ii) what algorithmic approaches are best at identifying immunogenic neoantigens. In particular, I will describe new results from our consortium effort in this area, the Tumor Neoantigen Selection Alliance.

3:00 Sponsored Presentation (Opportunity Available)

3:30 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

4:15 Beyond Cancer Neoantigens: Shedding Light on Antigenic Dark Matter with Proteomics

Joshua Eric Elias-Merriman, PhD, Assistant Professor, Chemical and Systems Biology, Stanford University

Although MHC-presented cancer neoantigens hold untapped potential to be highly specific immunotherapy targets, the extent to which discovery efforts can extend to all cancers, and to other diseases is unclear. In this talk, I will touch upon my lab’s proteomic strategy for characterizing antigens in multiple contexts including cancer, infection and autoimmunity, and our new tools that expand the range of antigens we can empirically discover.

4:45 In vivo Applications of Neoepitope-Based Vaccines

Jill Schartner, PhD, Scientist, Department of Translational Oncology, Genentech

This talk will discuss in vivo applications of neoepitope based vaccines, we will discuss how to determine dosing and scheduling in mice, T-cell infiltration, etc.

5:15 Neoantigen Targeted CD8 T Cell Responses via Optimized DNA Immunotherapy

Niranjan Y. Sardesai, PhD, Co-Founder, President & CEO, Geneos Therapeutics

Tumor neoantigen targeting has emerged as a viable approach for treating cancer. Beyond prediction and selection algorithms, neoantigen delivery platforms and platform potency are important considerations to drive neoantigen targeted immune responses in vivo. This presentation will discuss the plasmid DNA-based ASPIRE® platform for development of neoantigen targeted personalized cancer immunotherapy.

5:45 Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Day

Friday, March 15

8:00 am Registration Open and Morning Coffee

NEOANTIGENS TO GUIDE T CELL THERAPY AND VACCINE STRATEGY

8:25 Chairperson’s Remarks

Niranjan Y. Sardesai, PhD, Co-Founder, President & CEO, Geneos Therapeutics

8:30 The T Cell Repertoire Is Associated with Survival in Non-Small Cell Lung Cancer

Alex Reuben, PhD, Assistant Professor, Thoracic Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center

Tumor clearance is reliant on T cell responses. Therefore, we studied the T cell repertoire in patients with non-small cell lung cancer (NSCLC). Increased T cell heterogeneity was associated with shortened disease-free survival. Furthermore, a substantial proportion of T cells were shared between the normal lung and tumor and reactive to factors unrelated to the tumor. Our work sheds light on the challenges in harnessing T cell responses in NSCLC.

9:00 Personalized Adoptive Cell Therapies: NeoAntigen-Targeted T Cells against Cancer

Stefanie Mandl, PhD, Vice President, Translational Immunology PACT Pharma

Clinical benefit observed with immuno-oncology trials often depends on the unleashing of a pre-existing intrinsic T cell immune response in each cancer patient. The targets of these intrinsic T cells are now ascribed to recognition of patient-specific tumor neoantigens arising from cancer mutations. PACT Pharma has developed the ability to selectively capture neoantigen-specific CD8 T cells from peripheral blood (& from TILs) of the patient. Leveraging this technology, PACT Pharma is developing personalized, autologous neoTCR-engineered T cell therapies for the eradication of solid tumors.

9:30 The Discovery and Development of Novel Monoclonal Antibody, NEO-201 Targeting a Novel Neoantigen

Philip Arlen, MD, President & CEO, Precision Biologics, Inc.

Immunogenic neoantigens were derived from a membrane preparation of pooled allogeneic colorectal cancer from patients undergoing surgery. Membrane fractions were isolated and tested for immunogenicity and utilized in a clinical trial in patients with chemotherapy refractory metastatic colorectal cancer. A positive correlation was observed in patients who were able to mount and sustain IgG responses to vaccine. Antibodies were screened using this vaccine and tested for sensitivity, specificity, and anti-tumor function. A novel monoclonal antibody, NEO-201, has demonstrated preclinical antitumor function. A novel monoclonal antibody, NEO-201, has demonstrated preclinical antitumor activity with sensitivity and specificity to several tumor types.

10:00 Sponsored Presentation (Opportunity Available)

10:30 Coffee Break in the Exhibit Hall with Poster Viewing


FEATURED SESSION: PERSONALIZED CANCER VACCINE TRIALS

11:15 How the DNA Vaccine Format Used in a Novel Manner Can Generate Potent CD8-Dominated Neoantigen-Specific T Cell Responses

Agnete Fredriksen, PhD, President and CSO, Vaccibody

Vaccibody has a unique platform technology able to potentiate vaccines by attracting, activating and delivering antigens to antigen presenting cells. Recent clinical data indicate an important role of neoantigen-specific T cells in patients that benefit from immunotherapies. A vaccibody DNA vaccine opens up for a rapid and cost-effective manufacturing perfect to develop commercially viable patient-specific vaccines on demand. A clinical study using Vaccibody neoantigen vaccines in advanced cancer is ongoing.

11:45 Helper T Cell Epitope-Based Vaccines for Breast and Ovarian Cancer Treatment

Keith L. Knutson, PhD, Professor of Immunology, Director, Mayo Clinic Florida Discovery and Translation Labs, Cancer Research Program, Director, Mayo Clinic Cancer Center Immunology and Immunotherapy Program, Mayo Clinic

With over 265,000 new cases per year and over 50,000 deaths, breast and ovarian cancers represent a significant health burden in the USA. Prior work has demonstrated that CD4 helper T cell immunity is protective against recurrence of both breast and ovarian cancer. Based on pre-existent immunity, several degenerate epitope-based vaccines have been developed targeting tumor-associated antigens such as HER2/neu and the Folate Receptor Alpha. These vaccines demonstrate the ability to generate robust long-lived immunity and may have a role, when combined with other agents, in protecting against disease relapse.

12:15 pm Development of Glioma T Cell Therapy Targeting the Novel and Shared Neoantigen Derived from Histone 3 Variant H3.3K27M Mutation

Hideho Okada, MD, PhD, Professor of Neurological Surgery, University of California, San Francisco; Member, Parker Institute for Cancer Immunotherapy

The majority of diffuse midline gliomas, including more than 70% of diffuse intrinsic pontine glioma, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3. We have identified an HLA-A2-restricted neoantigen epitope encompassing this mutation, and isolated a high affinity T cell receptor. These data provide us with a strong basis for developing T cell–based therapy targeting this shared neoepitope.

12:45 Close of Symposium

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