Focus on Various Immunotherapeutic Treatment Strategies in Cancer Research
In the ongoing quest to revolutionize cancer treatment, several promising developments are underway. This article highlights three notable advances: Immunocore's IMCgp100, Celyad's CYAD-101, and Amgen's AMG-330.
Immunocore's IMCgp100, a therapy based on ImmTAC technology, is being developed for uveal melanoma by the company behind the Immunocore brand. The therapy targets the gp100 antigen presented in the context of HLA-A2 and is currently in a phase I trial. The trial has shown early evidence of tolerability and anti-leukemic activity, although efficacy is only seen at higher doses. Prolonged stable disease with reduced toxicity, as well as some partial and minor responses, have been reported in trials of IMCgp100.
A rash of grade 2 or above appears to be associated with a better response to IMCgp100 treatment. There is evidence for a potential overall survival benefit above the eight- to nine-month median overall survival typically seen with other therapies, although the data set is small. Long-term survival has been obtained, for example in one complete responder patient who is still alive at over 61 weeks. So far there has been no significant toxicity seen, and no GVHD with CYAD-101.
Celyad's lead therapy is CYAD-01: an NKG2D-based CAR T-cell therapy expressed on autologous T cells that is in phase I/II development. CYAD-101, an allogeneic version of CYAD-01, targets NKG2D ligands and contains a TCR inhibitory molecule to reduce the risk of GVHD. The allogeneic CYAD-101 is currently being assessed in the phase I alloSHRINK trial for unresectable colorectal cancer, with data due in the second half of this year. An excellent safety profile of the combination has been seen in the 48 patients treated so far, with the majority achieving clinical benefit.
Amgen's CD3/CD33 bispecific T-cell engager therapeutic AMG-330 is being tested in a phase I first-in-human trial for acute myeloid leukemia (AML). The main side effect seen has been cytokine release syndrome.
In addition to their lead therapies, both Celyad and Immunocore are developing next-generation non-gene-edited allogeneic CAR T-cell platforms. Celyad is using shRNA technology, while Immunocore continues to refine its ImmTAC technology.
Meanwhile, DNAtrix's tasadenoturev adenovirus therapy for glioblastoma has various regulatory designations, including Orphan status (U.S. and EU), Fast Track (U.S.), PRIME (EU) and PIM (U.K.). The therapy is currently being assessed in the CAPTIVE (KEYNOTE-192) trial in combination with Keytruda in glioblastoma patients at first or second relapse where no surgery is planned or possible.
These advancements represent significant steps forward in the fight against cancer, offering hope for patients and their families. As these treatments move through the clinical trial process, we eagerly await the results and the potential for improved outcomes for those battling this disease.
