Immunofoco has announced the publication of a preclinical study and an early clinical case report for IMC002 in Molecular Cancer Therapeutics, a peer-reviewed journal of the American Association for Cancer Research (AACR). The report includes a patient with unresectable, metastatic CLDN18.2-positive gastric cancer who achieved a pathological complete response (pCR) following IMC002 treatment.
IMC002 is an innovative CAR-T cell therapy that incorporates a nanobody-based antigen recognition domain targeting Claudin 18.2 (CLDN18.2), a tumor-associated antigen highly expressed in gastric and gastroesophageal junction cancers, as well as other solid tumors. The study provides robust preclinical evidence supporting IMC002’s potential in solid tumors, a field where conventional CAR-T therapies have faced significant challenges.
Previous studies have shown that CLDN18.2 CAR-T constructs based on conventional single-chain variable fragment (scFv) architectures can induce severe on-target, off-tumor (OTOT) toxicity and treatment-related mortality in preclinical models. IMC002 was specifically designed to overcome these limitations by using a single-domain heavy-chain variable region (VHH, or nanobody) as its antigen-recognition domain instead of a traditional scFv. Compared with scFv-based CARs, VHH domains have a lower tendency to oligomerize, reducing nonspecific CAR clustering and tonic signaling on the T-cell surface, and thereby mitigating premature T-cell exhaustion.
Consistent with this design, IMC002 demonstrated potent antitumor activity with a favorable safety profile in preclinical studies. In comprehensive in vitro and in vivo comparisons with multiple CLDN18.2 CAR constructs—including single-VHH, dual-VHH, and scFv-based candidates—IMC002 showed superior safety characteristics. Animals treated with IMC002 did not experience significant body weight loss or treatment-related mortality, and histopathological analyses revealed no severe tissue damage. These results indicate that IMC002 effectively reduces OTOT toxicity in normal tissues, such as the gastric mucosa and pancreas, while maintaining strong antitumor efficacy.
The publication also highlights a clinical case in which IMC002 treatment induced marked tumor regression, enabling subsequent radical surgical resection. Pathological examination of the resected tumor confirmed a pathological complete response (pCR), and treatment-related adverse events were mild and manageable.
“The efficacy and favorable safety profile of IMC002 observed in both preclinical studies and this clinical case are highly encouraging,” said Professor Jianming Xu, corresponding author of the study and Professor at the First Medical Center of the Chinese PLA General Hospital. “These findings validate the potential of highly specific nanobody-based platforms in CAR-T cell therapy and suggest that CLDN18.2-targeted CAR-T therapies could move beyond late-line settings, including neoadjuvant and adjuvant applications, to benefit a broader population of patients with gastric and pancreatic cancers.”
IMC002 is currently being evaluated in pivotal clinical trials in patients with CLDN18.2-positive solid tumors. Immunofoco remains committed to advancing next-generation CAR-T therapies to address unmet medical needs in solid tumor oncology.
