Building Personalized Vaccines and Technologies for Hematologic Malignancies and Solid Tumors
Cancer immunotherapy represents a paradigm shift in the treatment of multiple cancers including both solid and hematological malignancies. Despite the remarkable potency and clinical activity of modern immunotherapies such as checkpoint blockade antibodies and CAR-T therapies, not all cancers are responsive to these treatments, highlighting the intertumoral and intratumoral heterogeneity of these malignancies. Moreover, off-target immune-related toxicities further complicate these therapies. Increasing the specificity of immunotherapy has the potential to improve clinical responses and reduce autoimmune toxicities. Recent preclinical and clinical data support the feasibility of developing personalized vaccines targeting tumor-specific mutant neoantigens formed by genomic alterations acquired during cancer development and progression. Due to their exclusive tumor expression, neoantigens should avoid central tolerance and hence are attractive as therapeutic targets.
This session will focus on the emerging efforts to directly exploit neoantigens present in cancer. Speakers will discuss data demonstrating the therapeutic efficacy of personalized neoantigen vaccines in preclinical models and emerging findings from personalized vaccine clinical trials. Speakers will also discuss recent progress in refining approaches to select preferred antigenic targets and optimal vaccine platforms and how best to move forward with personalized vaccines used alone or in combination with other therapies.
Advances in oncology drug development have led to the recent approval of novel immunotherapies. Given as monotherapy or in combination with other drugs or cancer treatment modalities, oncology providers must increase their knowledge in immunotherapy, as the mechanism of action, patient education, and adverse event management differs from chemotherapy and targeted therapy.
This session focuses on the clinical management aspects of immunotherapy in oncology. Presentations by advanced practitioners will provide an opportunity for attendees to improve clinical outcomes for individuals receiving immunotherapy through effective patient education, assessment, and management strategies of immune-related adverse events (ir-AEs).
With a record number of abstracts submitted in 2017, three session have been dedicated to abstract presentations on clinical trials:
- High Impact
- New Agents
- Novel Combinations
These session include a combination of regular and late-breaking abstracts on the latest clinical trials.
Economics of Immunotherapies and Immunotherapy Combinations
Tumor immunotherapy approaches that have shown the most recent promise have included the checkpoint inhibitors and adoptive cellular therapy (ACT). Checkpoint inhibitors that block the PD1 pathway have shown anti-tumor activity in over 20 different types of cancer and within the last 3 years have received FDA approval for 9 distinct cancer types as well as a subset of tumors from multiple tumor types that exhibit microsatellite instability. The success of this approach has prompted the launch of over a thousand studies of combinations of PD1 pathway blockers with other immunotherapies, targeted therapies, radiation and chemotherapy and even ACT. In addition, PD1 pathway blockers have also shown anti-tumor activity in the adjuvant setting in melanoma and are currently being studied in this setting in multiple tumor types. ACT has also shown activity in a many tumor types with the administration of cells with a chimeric antigen receptor against CD19 (CD19-CARs, KymriahTM) recently receiving FDA approval for the treatment of patients with acute lymphocytic leukemia. In contrast to checkpoint inhibitors which are administered over time with repeated dosing, ACT is generally administered as a single infusion with the potential for long term clinical benefit. Similar to checkpoint inhibitors, the success of CD19 CARs have prompted research into further modulation of T Cells ex-vivo including the use of CRISPR technologies to KO inhibitory checkpoint on the adoptively administered T cells.
These novel therapies are marketed at a very high prices and the newer approaches and combinations could raise the costs even higher potentially putting a tremendous strain on already challenged health care systems. On the other hand, CD19-CARs, have been frequently characterized by durable responses and prolonged treatment free interval/survival in a growing subset of patients raising the potential that these treatments could change cancer from a rapidly lethal to a curable disease in many patients. Balanced against this are a very different pattern of adverse events compared to traditional cytotoxic chemotherapy or targeted therapies with acute toxicities that require aggressive management and occasionally lead to chronic effects (less so for ACT) that require management over an increasingly extended lifetime. Taken together these factors cause immunotherapy to fall outside the value frameworks being created for more traditional oncology treatments.
This session will discuss the some of the unique economic issues arising from cancer immunotherapy (both checkpoint inhibitors and ACT) and highlight some distinct approaches to determining their value relative to other treatments. It is envisioned that the presentations will provide a fresh perspective on the value proposition in immunotherapy, encourage discussion on how best to portray the benefits and risk of immunotherapy, identify gaps in our knowledge base and stimulate further research toward addressing these.
Emerging Models & Imaging
In this session, the speakers will address the emerging methods for collection of high-resolution, multiplex optical imaging data on the tumor environment, the combination of these methods with other measurement tools such as RNA transcriptomics, and new tools for analysis of the data resulting from such analyses. Issues such as the number, distribution, phenotypic state, and subset origin of lymphocytes, myeloid cells, malignant cells, and stromal cells in the tumors will be discussed, along with the importance of quantitative description of the cancer cell, stromal, and immune cell spatial distributions in and around the tumor site. The talks will show application of these methods and tools can improve patient care by providing insight into immunotherapy choices, while also guiding research into improved treatments.
Energizing Immune Cell Metabolism in Cancer
Immunotherapies designed to trigger T cell destruction of tumor cells can result in sustained and complete responses in patients whose cancers were resistant to available treatment options. Evidence suggests that how T cells generate energy in the tumor microenvironment plays an important role in their effectiveness. Furthermore T cell metabolism can be modulated to improve their anti-cancer activities. In this session, speakers will discuss the key metabolic properties of anti-cancer T cells, along with potential strategies to enhance T cell immunotherapy through metabolic modulation.
Genetically Modified Cell Therapy
Genetically modified immune effector cells have shown tremendous promise in patients with B cell malignancies. This session will review the latest updates in chimeric antigen receptor based T cell therapies for hematologic malignancies and the latest developments of engineered cell therapies, including new applications in solid tumors and combinations with gene editing technologies. Speakers will also discuss the recent progress toward commercialization and widening availability of genetically modified cell therapies.
Hot Topic Symposium: Advancing the Field: Can Physics and Mathematics Impact the Development of Tumor Immunotherapy?
Tumor immunotherapy has evolved into a standard therapeutic strategy for the treatment of cancer and revolutionized cancer care. Yet the underlying biological principles of tumor immunology, immuno-oncology drug resistance and rationale for rapid combination/sequential drug development are lacking. Recently the physical science community has begun to study the immune system as an example of a complex adaptive process; these studies have been enabled by progress in sequencing technology and by progress in the application of non-equilibrium statistical physics to living systems. In this Hot Topic Symposium we will bring together leading authorities in tumor immunology, physics and mathematics to provide an overview of the top priorities in tumor immunotherapy and the latest advances in physical science that might impact further drug development and biologic understanding for the field. The symposium will identify the major areas for convergence between physical sciences, systems biology and tumor immunology. Participants should find the discussion provocative and will have an opportunity to influence further integration among experts in these disciplines to influence more rapid development of tumor immunotherapy for patients with cancer.
Mechanisms of Acquired Resistance to Immunotherapies
Most tumor responses to immunotherapy are long lasting. However, in approximately 30% of patients treated with anti-CTLA4 or anti-PD-1 blockade for melanoma, and a higher frequency for epithelial cancers, relapse after a period of objective tumor response is observed. This session will discuss why understanding the molecular mechanisms of these instances of acquired resistance is important to be able to develop new approaches to prevent or treat resistance. Speakers will also review initial studies performing large scale genomic comparisons between baseline and relapsed lesions that provide evidence of defined pathways guiding acquired resistance to checkpoint inhibitor immunotherapy.
Oncolytic Viruses and Intratumoral Therapies
Oncolytic viruses have considerable potential for contributing to cancer immunotherapy as single agents and as part of combination regimens. Oncolytic viruses are native or modified viral vectors that selectively replicate in and kill tumor cells while promoting host anti-tumor immunity. Recently, the first oncolytic virus, an attenuated herpes simplex virus type 1 (HSV-1) encoding GM-CSF, was approved for the treatment of patients with advanced melanoma. In addition, to HSV-1, there are many other viral species that can mediate tumor killing and vectors can be genetically modified to reduce pathogenicity, limit viral immunogenicity, enhance anti-tumor immunity, and deliver gene therapy to target the tumor. This session will highlight pre-clinical developments designed to optimize oncolytic virus therapy and will report significant new clinical data related to oncolytic viruses currently in clinical development.
Science Behind the Therapy: Mechanisms of Efficacy & Toxicity
This session will address immune related adverse events associated with checkpoint inhibitors as well as host factors that may affect these therapies. Immune related adverse events are not uncommon, and may shed light not only on the mechanisms of the drugs in patients with cancers, but also help in understanding the mechanisms of spontaneous immune-mediated diseases. In addition, environmental factors including the microbiome and host-specific factors may be determinants of the outcomes of therapies and may be important in designing personalized approaches.
Tumor Immunology 101
This session, presented by leading authorities in tumor immunology and cancer immunotherapy, is specifically designed for nurses, pharmacists, oncologists, and others involved in treating cancer patients with immunotherapy. The presentations provide an overview of basic immunology, tumor immunotherapy principles, and discussion about what is on the horizon for cancer immunotherapy.