Autologous engineered T cell receptor therapy in advanced cancer.
Apostolia-Maria TsimberidouMehmet A BaysalAbhishek ShankarBorje S AnderssonPublished in: Human vaccines & immunotherapeutics (2023)
To overcome challenges associated with adoptive cell therapy (ACT), we developed a personalized autologous T-cell therapy program. Patients with advanced cancer with HLA-A *02:01 allele and tumor expression of PRAME, MAGEA1, MAGEA4, MAGEA8, NY-ESO-1, COL6A3 exon 6, MXRA5, and/or MMP1 underwent leukapheresis and T-cell product manufacturing. Patients received lymphodepletion, IMA101 infusion and interleukin 2 for 14 days. Of 214 screened patients, 14 were treated (6, IMA101; 8, IMA101 and atezolizumab). The most common adverse events were cytokine release syndrome (G1, n = 6; G2, n = 4) and cytopenia. At 6 weeks, 12 (85.7%) patients had stable disease. Three patients had prolonged disease stabilization for 12.9, 7.3, and 13.7 months, respectively. The median progression-free survival and overall survival were 3.4 months and 9.4 months, respectively. Target-specific T cells expanded to constitute up to 78.7% of CD8+ cells. In conclusion, IMA101 was feasible and well tolerated, leveraging the potential of multi-targeted ACT that warrants further investigation.
Keyphrases
- cell therapy
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- advanced cancer
- palliative care
- prognostic factors
- peritoneal dialysis
- stem cells
- poor prognosis
- bone marrow
- free survival
- long non coding rna
- cell proliferation
- low dose
- induced apoptosis
- patient reported outcomes
- signaling pathway
- climate change