Yongwoo D. Seo, MD
Fellow
MD Anderson Cancer Center
Houston, Texas, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Soft tissue sarcomas (STS) are heterogeneous tumors which are morbid and lethal. G100 is a stable oil-in-water emulsion of glucopyranosyl lipid adjuvant, a potent TLR4 agonist, which has been utilized as vaccine adjuvants without toxicity. We hypothesized IT G100 would induce robust local and systemic anti-tumor immune response in the STS tumor microenvironment (TME), leading to improved outcomes.
Methods:
15 metastatic STS patients with a superficial injectable lesion were treated with weekly IT G100 for 8-12 weeks plus concurrent radiotherapy. Core biopsies and blood were collected pre and post treatment, and immune analysis was performed by T cell receptor (TCR) sequencing and multiplex IHC. RECIST v1.1 and CTCAE guidelines were used to monitor clinical outcomes.
Results:
No grade 3 or higher treatment-related toxicity was observed, and local tumor control was achieved in 93% (14/15). 6 (40%) had overall stable disease after IT G100, and 1 (#5-6) had complete regression of injected tumor. 3 other patients had long term control of injected tumor past 250 days, during which the uninjected STS had progression despite radiation.
In patients with durable local control after IT G100, multiplex IHC demonstrated increased CD4 and CD8 T cell infiltration, as well as decrease in regulatory T cells. In #5-6, TCR sequencing revealed 5-fold increase in PBMC clonality, with selective clonal expansion of T cells present in pre-treatment biopsy. In #10-6 (local control to 370 days), there was clonal expansion of T cells within TME which were also found in post treatment PBMC; matched single cell sequencing revealed these clones to be CD4 T cells with Th1 gene signatures.
Conclusions:
IT G100 represents a viable agent for local control of metastatic STS, appearing to shift the TME into a more inflammatory state with infiltration of T cells. There was selective expansion of clones present in pre-treatment TME in circulating PBMC post IT G100, isolated to be Th1 cells in one patient. This suggests induction of adaptive anti-tumor response, which may further be enhanced by combination with other immunomodulators.