We will see over the next few years. CREATE Medicines plan to test multi-immune cell activation by engaging T-cells and NK cells with myeloid cells (using mRNA). The latter showed that single-agent CAR+ myeloid cells infiltrated tumours and this resulted in endogenous T-cell (and NK) infiltration and checkpoint upregulation.
Another will test a dual armoured anti-CLDN18.2 CAR-T (using a lentiviral vector). They showed that it had greater antitumour efficacy at lower doses than benchmark designs, including unarmoured-, TGFBRIIDN-armoured, and IL-15-armored versions. Mechanistically, the armours increase T-cell infiltration, cytotoxicity, and expansion. However, they are using an in vivo spatial pooled screening platform, but two others that built their own platforms have failed when testing different CAR-T's in humans.
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