Iovance Biotherapeutics Inc (IOVA)

[jondoeuk]

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].

Refs:
1 https://www.jci.org/articles/view/73639
2 https://www.nature.com/articles/s41586-018-0130-2
3 https://www.nature.com/articles/s41467-018-05072-0
4 https://onlinelibrary.wiley.com/doi/full/10.1002/cyto.a.22351

* 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.