Alaunos Therapeutics Inc (TCRT)

[jondoeuk]

I think a better video is Demystifying Medicine. At around the 53 minute mark Dr. Rosenberg says the reason why vaccines have failed is because they don't generate enough T-cells to impact the cancer and you can't get rid of enough Tregs, MDSCs and M2 macrophages. Also, (in my view) he forgot about targets [1].

To address the first problem GRTS is using a heterologous prime-boost vaccine. Preclinical data show this not only induces a T-cell response which is comparable to different adoptive cell transfer treatments, but also the cells persist longer [2]. The early human data (more will likely be presented at AACR and ASCO) are pretty encouraging [3].

The second can be dealt with via mAbs and/or small molecules (that deplete and/or reprogramme) which are in development.

As for the third the company tested its selection platform (which they continue to improve) against public methods and looked at how both compared to the tandem minigene approach used by Dr. Rosenberg/US NCI [4]. For the top twenty MHC Class I restricted neoantigens we know the majority (19/26, 73%) would be included vs. only 9/26 (35%) with public tools. Sometime this year they plan to incorporate MHC Class II restricted neoantigens in their vaccines as the dataset and model for these targets will be sufficiently robust. This should improve the efficacy [5] and will try to prioritise clonal neoantigens [6].

In addition, they have a deal with BLUE [7].

Refs:
1 https://videocast.nih.gov/summary.asp?Live=30267&bhcp=1
2 https://cancerres.aacrjournals.org/content/78/13_Supplement/724
3 https://www.fiercebiotech.com/biotech/gritstone-posts-one-most-potent-immunogenic-responses-for-a-neoantigen-vaccine
4 https://www.nature.com/articles/nbt.4313
5 https://www.nature.com/articles/s41586-019-1671-8
6 https://science.sciencemag.org/content/351/6280/1463
7 https://www.businesswire.com/news/home/20180823005039/en/bluebird-bio-Gritstone-Oncology-Announce-Strategic-Collaboration