CLN-619, a MICA/B monoclonal antibody that promotes innate immune cell-mediated antitumor activity

Background
Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for the natural killer group 2 member D (NKG2D) receptor and are broadly expressed on tumor cells but minimally on normal tissues. When cytotoxic NKG2D-ex…

Plasticity of tumor cell immunogenicity: is it druggable?

This short perspective presents, at a high level, some observations and speculations about cancer immunotherapy that derive from experiences at the Dana-Farber Cancer Institute and the Novartis Institutes of Biomedical Research.

Discovery and validation of frameshift-derived neopeptides in Lynch syndrome: paving the way for novel cancer prevention strategies

Background
Lynch syndrome (LS), caused by germline pathogenic variants in the mismatch repair genes, leads to high rates of frameshift-derived neopeptide (FSDN) expression due to microsatellite instability (MSI). While colorectal cancer (CRC) preventi…

MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence

Background
Chimeric antigen receptor T cell (CAR-T)-based immunotherapies have reshaped the therapeutic landscape of cancer treatment, in particular for patients afflicted with leukemia. However, defects in CAR behaviors and clinical complications hav…

Novel PD-1-targeted, activity-optimized IL-15 mutein SOT201 acting in cis provides antitumor activity superior to PD1-IL2v

Background
SOT201 and its murine surrogate mSOT201 are novel cis-acting immunocytokines consisting of a humanized/murinized/, Fc-silenced anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) fused to an attenuated human interleukin (I…

CD22-targeted chimeric antigen receptor-modified T cells for children and adults with relapse of B-cell acute lymphoblastic leukemia after CD19-directed immunotherapy

Background
Relapse of B-cell acute lymphoblastic leukemia (B-ALL) with CD19-antigen loss after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has a dismal prognosis. Novel immunotherapeutic strategies for this patient population are urge…

Past failures and new horizons: the nuances of tertiary lymphoid structures in high-grade serous ovarian cancer may contribute to immunotherapy effectiveness

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that allow for optimal B-T cell crosstalk in solid tumors. Further, TLS are found in many solid tumors and are associated with improved patient survival and superior immunotherapeutic …

Shp-1 regulates the activity of low-affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition

Background
The presence of activated CD8 T cells in the tumor microenvironment is correlated with an effective immune response to immune checkpoint inhibitor (ICI) therapy. However, ICI predominantly targets high-affinity T cells, which may be less ab…

T-bet overexpression enhances CAR T cell effector functions and antigen sensitivity

Background
T cells modified to express a chimeric antigen receptor (CAR) are successful against B-lineage malignancies but fail to induce durable remissions in up to half of patients and have shown limited efficacy against other types of cancer. Strat…

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