SAN DIEGO, California, United States — October 27, 2026
Calidi Biotherapeutics, Inc., a biotechnology company developing targeted genetic medicines, announced new preclinical findings from its RedTail platform at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid. The two poster presentations highlighted advances in CLD-401, an investigational virotherapy designed to stimulate antitumor immunity, and the company’s in situ T-cell engager (TCE) platform for solid tumors. In an EMT6 breast cancer mouse model, a single dose of CLD-401 produced tumor regression and complete tumor eradication in 80% of treated animals, compared with no complete responses in the control group. Separately, Calidi reported that its EpCAM-targeted TCE candidate generated approximately 10 ng/mL of TCE directly within tumors following intravenous delivery of the engineered virotherapy, without administering the TCE protein systemically. The findings support further investigation of RedTail’s potential to deliver therapeutic genetic payloads to tumors and create localized immune activity, although the results remain preclinical.
CLD-401 Shows Antitumor Activity Across Preclinical Tumor Models
CLD-401 is Calidi’s lead RedTail program, designed for systemic administration to selectively target tumors and express an interleukin-15 superagonist (IL-15 SA), a potent activator of T cells and natural killer (NK) cells. At ESMO 2026, the company reported that a single dose led to complete tumor eradication in 80% of mice bearing EMT6 breast tumors, compared with 0% in the control group. Additional findings from an MB49 bladder cancer model showed antitumor activity following both intravenous systemic delivery and direct intratumoral administration, suggesting potential flexibility across different tumor-accessibility settings. The engineered virotherapy is intended to reshape the tumor microenvironment by recruiting and activating immune cell populations, including NK cells, natural killer T cells and gamma delta T cells. Calidi is developing CLD-401 for metastatic non-small cell lung cancer, head and neck cancer and other tumor types with significant unmet medical needs. The program remains in investigational new drug (IND)-enabling development, and its efficacy and safety have not yet been established in human clinical trials.
In Situ TCE Platform Aims to Produce Immune-Engaging Proteins Inside Tumors
Calidi also presented preclinical data on CLD-501, its TROP-2-targeted candidate, and CLD-502, its EpCAM-targeted candidate. Both are systemically delivered RedTail virotherapies designed to selectively target tumors and locally co-express a tumor-targeted TCE alongside IL-15 SA. TCEs are engineered molecules that help bring T cells into contact with cancer cells expressing a specific target, promoting targeted immune-cell activity. In the reported studies, the TROP-2- and EpCAM-targeted constructs demonstrated antigen-dependent, dose-responsive T-cell-mediated cytotoxicity. The EpCAM-targeted construct also generated approximately 10 ng/mL of TCE directly within tumors following intravenous delivery of the platform, without requiring systemic administration of the TCE protein itself. Calidi further reported that adding a second TCE payload did not reduce expression of the co-encoded IL-15 SA in the in vitro and in vivo studies described. These findings suggest the platform may support localized production of multiple immune-modulating payloads within tumor tissue.
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RedTail Platform Seeks to Address Challenges in Solid Tumor Immunotherapy
Systemically administered TCE therapies can face challenges involving treatment-related toxicity, achieving sufficient exposure within tumors and the immunosuppressive tumor microenvironment. Calidi’s in situ approach is designed to address these barriers by using an engineered enveloped oncolytic virus to deliver genetic instructions to tumor sites, where therapeutic proteins can be produced locally. The RedTail platform is intended to help the virus evade immune clearance during systemic delivery, reach metastatic tumor locations, induce tumor lysis and express therapeutic payloads. The ESMO findings broaden the platform’s reported preclinical capabilities, spanning immune priming with CLD-401 and localized T-cell redirection through CLD-501 and CLD-502. However, the reported outcomes do not yet demonstrate clinical benefit in patients, and further research will be needed to establish the candidates’ safety, biodistribution, durability and therapeutic potential. Calidi stated that it is continuing to expand the platform’s functionality and pursuing strategic partnerships to support clinical development and broaden the potential application of its targeted genetic medicine programs.
Source:Calidi Biotherapeutics Press release
