Blogs

Cancer immunotherapy clinical trials to support urgently needed access in low and middle-income countries: a report from the SITC global access and impact committee

Summary:

David R. Kaufman from Third Rock Ventures served as the senior author on this SITC commissioned multi-authored piece, demonstrating the breadth of the ecosystem, along with many senior academics and representatives from Mexico, Ivory Coast, Nigeria, Brazil, Ghana, Uganda, and Cameroon. Other industry representatives from BIO Ventures for Global Health, Regeneron, Roche, and BeOne added their sense of how to drive the next steps in making IO available. Several issues ranging from creating the infrastructure to conduct clinical trials and provide local training and clear instruction in toxicity identification, and regulatory concerns, use of lower doses, and community engagement are thoughtfully explored. Critical issues of insurance coverage, cost, and getting broader participation in potentially life-saving therapies were explored. 

Mapping immune activity in HPV-negative head and neck squamous cell carcinoma

SITC vision: Opportunities for deeper understanding of mechanisms of anti-tumor activity, toxicity, and resistance to optimize cancer immunotherapy

This multi-authored manuscript includes senior authors Ryan Sullivan, an academic from Harvard, and Charlie Garnett-Benson at Bristol Myers Squibb (and a host of other clinician scientists) focused on essentially what comes next in our burgeoning field of IO. Their work highlights critical issues of defining response, mechanisms of resistance (both tumor intrinsic and extrinsic) based on murine models and clinical experience, and heightened sensitivity to toxicity issues. Additionally, how the patient participates in clinical trials and subsequent approved therapies brings needed attention to several areas. Initially, successes in novel therapies, including the application of cytokines such as IL-2, IL-15, and interferon alpha, dendritic cell vaccine, blocking of four immune checkpoints (CTLA-4, PD-1, PD-L1, LAG-3), three distinct varieties of adoptive cell transfer (ACT), infectious agents directed to the tumor (BCG, TVEC), and T-cell engagers (TCEs) targeting tumor-associated antigens (gp100, DLL3) were highlights for me. These therapies target both liquid and solid tumors.

Systematic identification and targeting of master regulator checkpoints (MRC) governing tumor microenvironment-mediated immune evasion

Summary: 

As an interesting convolution of single-cell and spatial transcriptomics, colleagues from Columbia University and DarwinHealth (Editor’s note: They have served as consultants on a grant I submitted last year.) have evolved an important approach to identifying consorts of genes and pathways that serve as important checkpoints in the immunotherapy of cancer. This group, in part funded through the Chan Zuckerberg Biohub, have developed a series of insights focused on these so-called Master Regulator Checkpoints (MRC). The highly evolved intratumoral cellular subpopulations, including regulatory T cells, cancer-associated fibroblasts, and tumor-associated macrophages, are thought to be hyperconnected by paracrine signals. Identification of these MRCs requires two major steps: 1) application of the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and 2) engaging the Virtual Inference of Protein-Activity by Enriched Regulon (VIPER) algorithm to identify proteins governing transcriptional cell states. These, in turn, can allow pharmacological targeting of pathways rather than individual ligand receptor pairs. Much of this allows the identification of available and testable small molecules, focusing on transcriptional programs rather than single targets. This fluid interaction between philanthropic organizations, traditional academe, and emergent biotech firms is well-illustrated here.