What question did this study set out to answer?

To enhance anti-PD-1 therapy efficacy by targeting the non-canonical immune checkpoint MUC1-C in solid tumors.

April 5, 2026

Abstract 1560: Targeting the non-canonical immune checkpoint MUC1-C enhances anti-PD-1 therapy in solid tumors

Key Points

To enhance anti-PD-1 therapy efficacy by targeting the non-canonical immune checkpoint MUC1-C in solid tumors.
Utilized syngeneic tumor model with MC38-hMUC1 colon adenocarcinoma cells expressing human MUC1
Combined anti-PD-1 therapy with PAb001, a humanized IgG1 antibody targeting MUC1-C
Evaluated tumor growth inhibition (TGI) using combinatorial treatment strategy
Achieved tumor growth inhibition of 91.3% with the dual-checkpoint blockade
Observed robust antitumor activity in the treated tumor models
Identified potential for additional anti-MUC1 antibodies to enhance treatment protocols

Abstract

Abstract Immune checkpoint inhibitors (ICIs), particularly monoclonal antibodies targeting PD-1 and PD-L1, have revolutionized cancer therapy by enhancing antitumor immune responses. Despite their clinical success across multiple tumor types, several challenges remain, such as suboptimal response rates, which underscores the need for novel combinatorial strategies. MUC1-C, a transmembrane glycoprotein aberrantly expressed in many cancers, has recently emerged as a non-canonical immune checkpoint associated with T cell depletion and dysfunction within tumor microenvironment, thereby promoting immune evasion. Here, we present a novel immunotherapeutic strategy that concurrently targets canonical and non-canonical immune checkpoints by combining anti-PD-1 with PAb001, a humanized IgG1 antibody developed by Peptron that binds MUC1-C with high affinity (KD 1 nM). In a syngeneic tumor model utilizing MC38-hMUC1, a murine colon adenocarcinoma cell line engineered to express human MUC1, combinatorial treatment with 1H7 (a surrogate murine antibody targeting human MUC1-C) and an anti-mouse PD-1 antibody exhibited robust antitumor activity, resulting in marked tumor growth inhibition (TGI = 91.3%). Ongoing studies are evaluating the combinatory efficacy of additional anti-MUC1 antibodies and ICIs to further define the selective advantages of PAb001 in treating malignant tumors, and are also aimed at elucidating the molecular mechanisms underlying its therapeutic activity. In conclusion, these findings support the therapeutic potential of a dual-checkpoint blockade strategy that concurrently targets canonical and non-canonical pathways, which offers a promising approach to address limitations inherent to current ICI-based therapies. Citation Format: Dae Young Kim, Hee Young Kang, Young Ha Yoon, Sung Min Kim, Hoil Choi, . Targeting the non-canonical immune checkpoint MUC1-C enhances anti-PD-1 therapy in solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1560.

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