SEP 27, 2017 12:00 PM PDT

Enhancing Checkpoint Blockade in Lymphoma with In Situ Vaccination

Presented at: Cell Biology 2017
Speaker
  • Assistant Professor, Hematology and Medical Oncology Director, Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai
    BIOGRAPHY

Abstract

Checkpoint blockade therapy for cancer has had tremendous impact on clinical outcomes, yet only a subset of patients respond. Recent studies show that response to checkpoint blockade does not always correlate with tumor-associated antigen (TAA) load and so must be determined by factors beyond mutational burden. This suggests that checkpoint blockade is limited by suboptimal cross-presentation of TAA by activated dendritic cells (DC) and will be potentiated by recruitment, loading and activation of cross-presenting DC at the tumor site.

To test this hypothesis, an early-phase trial (NCT01976585) in low-grade lymphoma was carried out testing a unique in situ vaccine (ISV) combining: 1) fms-like tyrosine kinase 3 ligand (FLT3L) to recruit DC, 2) radiotherapy to load FLT3L-mobilized DC with TAA, and 3) toll-like receptor agonist (TLRa) to activate TAA-loaded DC for cross-presentation. Strikingly, Brody and colleagues found partial and complete systemic tumor regressions at distant, untreated tumors. They also found specific elimination of malignant B cells with sparing of healthy B cells, suggesting a systemic anti-tumor immune response.

This data prompted a new trial in which anti-PD1 monoclonal antibody (mAb) and ISV (used to increase efficacy) are combined with a novel immune-monitoring approach involving co-administration of "surrogate antigens (Ag)" at the ISV site. The approach is being applied to multiple cancer types, including breast, head and neck, melanoma and sarcoma.

In this webinar, Brody will discuss these studies, including the key role mass cytometry played in defining the effects of treatment on the intratumoral and systemic immune repertoire with high resolution and in profiling the distinct checkpoint/co-activator molecules on TAA-specific, surrogate-Ag-specific and bulk CD8 T cells.


Show Resources
You May Also Like
MAY 17, 2022 9:00 AM PDT
MAY 17, 2022 9:00 AM PDT
Date: May 17, 2022 Time: 9:00am (PDT), 12:00pm (EDT), 8:00pm (CEST) Gene therapeutics have great potential to treat many severe diseases in an unprecedented, targeted manner. The biopharmace...
NOV 17, 2021 8:00 AM PST
C.E. CREDITS
NOV 17, 2021 8:00 AM PST
Date: November 17, 2021 Time: 8:00am (PDT), 11:00am (EDT) From waste disposal to promising biomarkers and therapeutic agents, exosomes and other extracellular vesicles are valuable in resear...
APR 28, 2022 8:00 AM PDT
APR 28, 2022 8:00 AM PDT
Date: April 28, 2022 Time: 8:00am (PDT), 11:00am (EDT), 5:00pm (CEST) Human pluripotent stem cells (PSCs) and their derivatives hold great potentials in...
DEC 01, 2021 7:00 AM PST
C.E. CREDITS
DEC 01, 2021 7:00 AM PST
Date: December 01, 2021 Time: 7:00am (PST), 10:00am (EST) In the era of immuno-oncology, there is a growing need for the identification of new biomarkers predictive for sensitivity to anti-P...
APR 26, 2022 7:00 AM PDT
C.E. CREDITS
APR 26, 2022 7:00 AM PDT
Date: April 19, 2022 Time: 7:00am (PDT), 10:00am (EDT), 4:00pm (CEST) High-content (HC) phenotypic profiling approaches are a powerful tool to study the effect of biological, genetic, and ch...
NOV 30, 2021 11:00 AM PST
C.E. CREDITS
NOV 30, 2021 11:00 AM PST
Date: November 30, 2021 Time: 11:00am (PDT), 2:00pm (EDT) In the recent years, measurable residual disease (MRD) assessment on multiple myeloma patients has gained increasing relevance. After...
SEP 27, 2017 12:00 PM PDT

Enhancing Checkpoint Blockade in Lymphoma with In Situ Vaccination

Presented at: Cell Biology 2017


Show Resources
Loading Comments...
Show Resources