1955P - Glycan-programmed T cell immunity: Effective adoptive T cell transfer in a CRC preclinical model

Background

Tumors exhibit a unique truncated glycan-landscape that influences immune responses through lectin-receptors to steer immune cells. So far, the mode-of-action behind GNU101 glycopeptides efficacy against colorectal cancer augmenting the effectiveness of conventional ICI immunotherapies (ESMO2023#4317) was unclear. This promising therapy warrants investigation to reveal the immunological response driving anti-tumor immunity.

Methods

In a syngeneic therapeutic model, C57BL/6 mice received s.c. MC38 cell injections. Treatment with 3% GNU101 in drinking water and/or anti-PD1 injections began on day 6. After 15 days, tumors were harvested, and T cells isolated and expanded from tumor tissues. These T cells, along with controls, were then intraperitoneally injected into untreated recipient mice alongside subcutaneous tumors and monitored for 2 weeks.

Results

T cells harvested from tumors of GNU101 or GNU101 with anti-PD-1 treated mice conferred anti-tumor responses, when transferred to treatment-naïve hosts. Those adoptively transferred T cells significantly reduced tumor growth. In mice receiving T cells from GNU101 combined with anti-PD-1 treatment, tumor growth was almost completely abolished. Conversely, T cells from healthy mice or from untreated tumor-bearing mice had no effect on tumor growth. Our data demonstrate that oral administration of glycopeptide formulation GNU101, mimicking the tumor glyco-code, provokes a highly specific anti-tumor T cell response. A long-lasting anti-tumor effect was transmissible into animals that were never exposed to GNU101. Upon T cell transfer, the response was highly tumor-specific and did not result in toxic effects or aberrant immune responses in other organs.

Conclusions

Potent, specific anti-tumor T cell response with long-lasting effects elicited by GNU101 uncover a new field in tumor biology. By provoking a distinct, tumor-specific response this formulation has clear benefits over approaches that result in the non-specific killing of fast proliferating cells (e.g. cytostatic drugs) or general immune activation (i.e. ICI treatment) that frequently provoke severe side effects. These findings underscore the potential of GNU101, as a promising immunotherapeutic cancer agent.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Gnubiotics Sciences SA.

Disclosure

Y. Miao, V. Lindenberg, Y. Adesokan, P.T. Asare: Financial Interests, Personal and Institutional, Full or part-time Employment, presently employed in Gnubtiocs sciences (producer of GNU101): Gnubiotics Sciences SA. M. Scharl: Financial Interests, Personal and Institutional, Financially compensated role, shares and is co-founder of Recolony AG, Zurich, CH, has shares in PharmaBiome AG, Zurich, CH, served as Advisor for AbbVie, Gilead, Fresenius, Topadur, Takeda, Roche and Celltrion, received speaker’s honoraria from Janssen, Falk Pharma, Vifor Pharma, Pileje, Phytolis and Bromatech and received research grants from AbbVie, Takeda, Gilead, Gnubiotics, Roche, Axalbion, Pharmabiome, Topadur, Basilea, MBiomics, Storm Therapeutics, LimmatTech, Zealand Pharma, NodThera, Calypso Biotech, Pileje, Herbodee, Vifor., MRS has shares in PharmaBiome AG, Zurich, CH,: Recolony AG ao. All other authors have declared no conflicts of interest.