There seems to be both a lack of clear understanding of TIL and any depth to the breadth in the reply.
Well, IOVA are using 'bulk' TIL, but in the (near) future plan to use a PD-1+ population [1].
However, it has been shown that CD39, rather than PD-1, accurately distinguish between reactive (CD39+) and unrelated (CD39-) CD8+ T-cell populations [2]. In line with the paper, another showed that co-expression of both CD39 and CD103 favoured the identification of tumour-reactive T-cells [3]. One company (AgonOx*) is working on the latter, and has a collaboration with PHIO.
Another problem is that on certain populations, such as neoantigen-experienced terminally differentiated effector memory cells, PD-1 is either not expressed, or expressed at very low levels [4].
* These double positive populations are highly enriched within both primary and metastatic lesions and have a broad repertoire of neoantigen-reactive TCRs. Also, they are able to find them in the majority of solid tumours sampled (~90%). The only difference is the frequency, with some higher, while others are lower.
More importantly, they can sort and culture as few as 2000-10,000 and grow them to billions in a five-week span. With improvements to ex vivo expansion, and using NKTR's bempeg over high-dose IL-2, the depth and duration of response should be greatly improved.
Initial indications could be SCHNC, NSCLC, melanoma, ovarian, RCC, bladder, cervical, HCC, prostate, breast, GBM and/or rectal.
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