Preprint Watch 2026-10-12: 6 Clinical Failures Flagged for PDCD1 | Claidex

Claidex Preprint Watch

doi:10.64898/2026.10.04.753375

Preprint WatchStrongOctober 12th, 2026

CXCR3 on transferred T cells enables vaccine-boosted adoptive T-cell therapy in solid tumors

Pereira Almeida, V.; Garner, L. C.; Abdel Malak, S.; Wicki, A.; McAuliffe, J.; Noblecourt, L.; Panetti, S.; Steffke, E. E.; Bhandari, A.; Yong, L.; Amini, A.; Hutchings, C.; Andreata, F.; Yang, Y.; Gerard, A.; Iannacone, M.; Fernandes, R. A.; Klenerman, P.; Van den Eynde, B.; Leung, C. S. K.

In a mouse adoptive T-cell therapy model, PD-1 blockade failed to improve outcomes while ChAdOx1 and MVA vaccination drove durable tumor regression through CXCR3-dependent recruitment of transferred T cells to the vaccine-draining lymph node.

Strong contradiction

6 prior failures

Three or more documented clinical failures match this mechanism, or a Phase 3 efficacy failure is on record.

The finding here is negative for PD-1 and it lines up with the Claidex record rather than contradicting it. The preprint reports that PD-1 blockade did not improve adoptive T-cell therapy in its model, while vaccine-driven CXCR3 ligand induction did. Claidex holds six terminated PDCD1 programs, four of them efficacy failures in settings where PD-1 blockade was added to an active backbone: first-line cervical cancer (camrelizumab-apatinib-pdcd1-first-line-cervical-cancer-phase2-efficacy-failure), castration-resistant and hormone-sensitive prostate cancer (pembrolizumab-enzalutamide-pdcd1-mcrpc-keynote-641-phase3-efficacy-failure, pembrolizumab-enzalutamide-pdcd1-mhspc-keynote-991-phase3-efficacy-failure), and adjuvant cutaneous squamous cell carcinoma (pembrolizumab-pdcd1-adjuvant-locally-advanced-cscc-keynote-630-phase3-efficacy-failure), with two further programs ended by sponsor decision (pds0101-pembrolizumab-pdcd1-hpv16-head-neck-versatile-003-phase3-strategic-reprioritization, js207-pdcd1-vegfa-post-platinum-nsclc-phase2-strategic-reprioritization). The common thread across the clinical failures and this preprint is that checkpoint release does not help when the limiting step is T-cell delivery to the tumor rather than T-cell exhaustion within it.

Abstract excerpt

Adoptive T-cell therapy (ACT) has demonstrated marked clinical benefit in hematological malignancies but has limited efficacy against solid tumors. Cancer vaccines can improve ACT, but the mechanisms underlying this combination are poorly understood. Here, we combined ACT with chimpanzee adenovirus ChAdOx1 (ChAd) and modified vaccinia Ankara (MVA) encoding tumor antigens. Whereas PD1 blockade failed to improve ACT, the combination with ChAd/MVA vaccination drove durable regression of established tumors, correlating with expansion of tumor-reactive T cells in lymphoid organs and increased tumor infiltration by T cells. Mechanistically, ChAd priming induced CXCR3 ligands (CXCL10 and CXCL9) in the vaccine-draining lymph node, thereby recruiting transferred T cells to this node independently of cognate antigen. CXCR3 expression on the transferred T cells, but not on host cells, was required for the anti-tumor effect of the combination therapy and favored T-cell accumulation in the vaccine-draining lymph node and the tumor. These findings identify CXCR3 on the transferred T cells as a determinant of ACT plus vaccination synergy and provide a rationale for combining viral-vector vaccines with TCR-T therapies, and for selecting or engineering T cells to retain CXCR3 expression.

Matching Claidex post-mortems

6 of 6 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.