Weekly Digests



Low LCOR allows cancer stem cells hide out

March 30, 2022

Triple-negative breast cancer (TNBC) is notoriously difficult to treat, and while anti-PD-1 and anti-PD-L1 immunotherapies are approved as treatment options, they are not particularly effective in this setting. Investigating immunotherapy resistance in TNBC, Pérez-Núñez et al. recently uncovered a novel tumor escape mechanism involving LCORlow cancer stem cells (CSCs) – and came up...

Improving GITR agonism with a bispecific

March 23, 2022

Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) signaling stimulates T cell activation and proliferation and can inhibit suppressive effects of regulatory T cells (Treg). However, agonistic GITR antibodies have shown limited results in the clinic, which may be due to limited receptor clustering-mediated signaling of this TNFR superfamily member. Therefore, Chan and Belmar...

TIGIT and PD-1 join forces to inhibit CD226 costimulation

March 16, 2022

Combination immune checkpoint blockade (ICB) therapies have been successful in the clinic, but the exact mechanisms of their synergy are not completely understood. For example, co-inhibition of PD-1 and TIGIT can be superior to either alone, although the distinct contributions of each to antitumor immunity remain unclear. Recently reported in Immunity, Banta and...

Tumor ‘B’ aware: tertiary lymphoid structures produce anti-tumor B cell immunity

March 9, 2022

While tertiary lymphoid structures (TLS), organized lymphoid structures found in sites of chronic inflammation and antigen exposure, have been implicated in improved outcome and response to immunotherapy in cancer, the role of B cell responses associated with these structures is not well known. Therefore, Meylan et al. studied the role of TLS on...

A bispecific targeting PD-L1 and 4-1BB shows potential from culture to clinic

March 2, 2022

Blockade of the PD-1/PD-L1 axis and stimulation of 4-1BB have been shown to enhance immune responses to cancer, and to synergize when used in combination. To maximize the potential for synergy, Muik et al. used the DuoBody technology platform to develop GEN1046, a full-length IgG1 bispecific antibody targeting PD-L1 and 4-1BB (with abrogated FcγR...

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