Tobemstomig, a novel bispecific antibody, preferentially blocks PD-1 and LAG-3 on CD8 TILs to expand stem-like T-cells for sustained tumor control

Checkpoint inhibitors targeting PD-1 have shown unprecedented efficacy in some cancer patients; however, co-expression of the immune-checkpoint LAG-3 by tumor infiltrating lymphocytes (TILs) might hinder such efficacy. PD-1 and LAG-3 are established markers of T-cell exhaustion in cancer and are co-expressed by stem-like CD8 T cells, a population critical for the response to anti-PD1 therapy, providing the rationale for their dual-blockade. Yet, blocking LAG-3 can lead to the expansion of regulatory T cells, reducing the efficacy of anti-LAG-3 therapy on CD8 TILs. To address this limitation, we developed tobemstomig, a novel bispecific antibody to preferentially and simultaneously block PD-1 and LAG-3 in cis on tumor-specific CD8 TILs, while sparing Tregs. It provided superior tumor growth inhibition in mouse models by replenishing stem-like cells and cytotoxic effector CD8 TILs, resulting in durable responses compared to monospecific antibodies targeting PD-1 and LAG-3 separately, which eroded the stem-like T cell pool over time.

Authors

Institutions

Publication Details

Journal
Cancer Research Communications
Published
2026-06-12
DOI
https://doi.org/10.1158/2767-9764.crc-26-0207
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Tobemstomig, a novel bispecific antibody, preferentially blocks PD-1 and LAG-3 on CD8 TILs to expand stem-like T-cells for sustained tumor control

António Peixoto, Carina Hage, Marina Bacac, Sara Colombetti et al.
Cancer Research Communications
Cancer Immunotherapy and Biomarkers
article

Tobemstomig, a novel bispecific antibody, preferentially blocks PD-1 and LAG-3 on CD8 TILs to expand stem-like T-cells for sustained tumor control

António Peixoto, Carina Hage, Marina Bacac, Sara Colombetti, Stéphane Leclair, Mario Perro, Silvia Jenni, Esther Bommer, Pablo Umaña, Tamara Hüsser, Merlind Mücke, Meher Majety, Stanford Chen, Laura Lauener, Klas Hatje, Christian Klein, Stefanie Briner, Valeria Nicolini, Laura Codarri Deak, Emilio Yángüez, Stefan Seeber, Sylvain Pilet, Iryna Dekhtiarenko, Sylvia Herter, Patrick A.A. Weber, Manuela Tanner, Thomas Höfer
article en

Abstract

Checkpoint inhibitors targeting PD-1 have shown unprecedented efficacy in some cancer patients; however, co-expression of the immune-checkpoint LAG-3 by tumor infiltrating lymphocytes (TILs) might hinder such efficacy. PD-1 and LAG-3 are established markers of T-cell exhaustion in cancer and are co-expressed by stem-like CD8 T cells, a population critical for the response to anti-PD1 therapy, providing the rationale for their dual-blockade. Yet, blocking LAG-3 can lead to the expansion of regulatory T cells, reducing the efficacy of anti-LAG-3 therapy on CD8 TILs. To address this limitation, we developed tobemstomig, a novel bispecific antibody to preferentially and simultaneously block PD-1 and LAG-3 in cis on tumor-specific CD8 TILs, while sparing Tregs. It provided superior tumor growth inhibition in mouse models by replenishing stem-like cells and cytotoxic effector CD8 TILs, resulting in durable responses compared to monospecific antibodies targeting PD-1 and LAG-3 separately, which eroded the stem-like T cell pool over time.

Cancer Research Communications
Roche (Switzerland) (CH), Université Fédérale de Toulouse Midi-Pyrénées (FR), German Cancer Research Center (DE), Vischer (Switzerland) (CH), Med Discovery (Switzerland) (CH)
Openalex Percentile: Top 7%
Cancer Immunotherapy and Biomarkers
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.