Junshi Biosciences Announces First-in-Class IL-2-Free TIL Therapy GC101 Demonstrates Robust Efficacy in Advanced Gynecologic Cancers in Landmark Publication in BMC Medicine

On May 20, Juncell Therapeutics and the team led by Director Cheng Zhongping from the Department of Obstetrics and Gynecology at Shanghai Tenth People's Hospital published an innovative research article titled "IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer" in the journal *BMC Medicine*. This marks the world’s first clinical report of TIL therapy that achieved favorable efficacy without the use of IL-2, signifying an important advancement and breakthrough for TIL therapy.

Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated promising clinical efficacy across various types of cancer, with a single administration potentially offering clinical cure or long-term survival benefits for patients with advanced cancer. On February 16 this year, the first TIL therapy was approved.FDAApproved for marketing and officially entering clinical application.

However, the clinical protocol for traditional TIL therapy is complex: before the infusion of TIL cells, high-dose chemotherapy lymphodepletion pretreatment is required; after the infusion of TIL cells, repeated injections of high-dose IL-2 are necessary. Patients must complete the treatment in a sterile ward or ICU, posing significant challenges to both medical institutions and patients.

Juncell Therapeutics has innovated the culture system of TIL cells, independently establishing the DeepTIL® technology platform. This platform enables the efficient culture of TIL cells without feeder cells and high concentrations of IL-2. Indicators such as culture success rate, cell quantity, cell viability, and anti-tumor activity all reach internationally leading levels. The obtained TIL cells (approved by the National Medical Products Administration, product code GC101) exhibit stronger in vivo adaptability and avoid dependency on high concentrations of IL-2. Therefore, prior to GC101 TIL cell infusion, only low-dose chemotherapy pretreatment is required (without reaching lymphodepletion levels); after cell infusion, there is no need for supplementary IL-2 injections, allowing patients to receive treatment in general wards, significantly enhancing the safety and accessibility of TIL therapy.

This study (NCT04766320) enrolled a total of 16 patients with recurrent, refractory gynecological conditions.Cancer PatientsAmong 14 evaluable patients (2 dropped out due to the COVID-19 pandemic), the median ECOG score was 2, with an average of 3.4 metastatic lesions and an average of 3.4 lines of systemic treatment received. 42.9% (6/14) of the patients had received standard-dose PD-1 antibody therapy and developed resistance. After TIL cell infusion therapy, no severe adverse reactions related to the cells were observed; 5 patients (35.7%) achieved objective response, with 3 patients achieving complete response that was long-lasting.

Clinical PK/PD studies show that, regardless of whether patients are resistant to PD-1 antibodies, using only 1/4 of the standard dose of PD-1 antibody to block PD-1 molecules on the surface of TIL cells, under low-dose preconditioning and without IL-2 injection, GC101 TIL cells can effectively survive and proliferate in patients, and this is positively correlated with efficacy.

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