Alaunos Therapeutics Inc (TCRT)

[jondoeuk]

This is very likely GILD's (under CRADA) https://clinicaltrials.gov/ct2/show/NCT03412877

Last year SGMO got an upfront payment of $150M from GILD and are eligible to receive up to $3.01B in potential milestones. They are working together on a program that creates both viral and non-viral methods to disrupt and insert certain genes into T and NK cells (both autologous and allogeneic (from healthy donors and induced pluripotent stem cells)), including the insertion of genes that encode CARs, TCRs and NKRs directed to up to ten mutually agreed targets. GILD is responsible for all clinical development costs and the commercialisation of any resulting approved product(s).

The first allogeneic product (from healthy donors) is an anti-CD19 CAR-T and a PhI trial should be open in 2H. The second is another allogeneic (again, from healthy donors) CAR-T targeting CD-19/20 (using a bicistronic vector, which allows for the expression of two different CARs on the same cell). It will use Hu19 [1], but I don't know when a PhI is going to start. A third product (unknown) is now moving forward. Based on this I would be surprised if a fourth wasn't in the works.

Once the neoantigen reactive TCR-T trial has more data they could move forward with others as GILD have their own method to screen patient TCRs for reactivity [2] and therefore don't need to rely on a tandem minigene library used by Dr. Rosenberg/US NCI. However, patients could lack T-cells with an adequate affinity due to TCR and other editing. To overcome such limitations, tumour-specific TCRs harvested from healthy donors could be used instead (they are likely working on this) [3].

Also, with synNotch T (and NK) cells can be engineered to locally produce a range of payloads, including pro-inflammatory cytokines and checkpoint antibodies. Given the flexibility of this, it should be possible for the cells to produce many, 'customised' for different cancer types. Some might act in concert with T or NK cell killing and others might act independently to remodel the immunosuppressive TME and engage the host immune system. Significantly, localised production should avoid the toxicities observed with systemic delivery and reduce costs [4].

In addition, the (CAR)NK cells could be used in patients whose cancer has become resistant to T-cell [5-7]. Data from another group shows activity [8].

Refs:
1 https://ashpublications.org/blood/article/132/Supplement%201/697/266071/Low-Levels-of-Neurologic-Toxicity-with-Retained
2 https://www.nature.com/articles/nm.3359
3 https://science.sciencemag.org/content/352/6291/1337
4 https://www.cell.com/fulltext/S0092-8674(16)31244-2
5 https://www.cell.com/cell/fulltext/S0092-8674(17)30065-X
6 https://www.sciencedirect.com/science/article/pii/S2211124719310502
7 http://jem.rupress.org/content/209/13/2351.long
8 https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(19)30097-8