EFFICACY AND SAFETY OF GENE THERAPYAND IMMUNOTHERAPY IN BREAST CANCER AND LEUKEMIA TREATMENT

Abstract

The immune system has a primary role against pathogens, including transformed cancer cells. However, cancer is associated with defective T cell function and reduced anti-tumour immunity. Conventional therapy, such as chemotherapy and radiotherapy, has failed to treat cancer efficiently and is mostly associated with systematic toxicity, off-target effects, and initiation of other types of cancer. The wide field of gene therapy and immunotherapy provide several promising treatment strategies that are anticipated to become powerful in preventing cancer-related death. Dendritic cell vaccine, suicide gene, and engineered TCRs are common gene immunotherapeutic strategies that have demonstrated limited toxicity and potent anti-tumour response in pre-clinical and clinical studies. The encouraging outcome of gene therapy and immunotherapy applications suggests a novel therapy for solid tumours and haematological malignancies. This systematic review was conducted to evaluate the safety and effectiveness of dendritic cell vaccine, suicide gene therapy, and engineered TCR in the clinical trials of breast cancer and leukaemia. “clinicaltrials.gov” and “PubMed” were used as search engines to identify all eligible clinical trials. A total of 438 records were identified and only seventeen clinical trials were selected eligible and included in this review. The risk of bias assessments was performed in every included study. The analysis illustrated that the use of a dendritic cell-based vaccine reduces the cancer residual and induce general immunity with no toxicity and limited adverse effects. The suicide gene therapy effect was mainly local in breast cancer and favourable in local refractory tumours. The studies reported severe adverse events and toxicity correlated with engineered TCRs therapy in breast cancer with limited immunity. i In conclusion, the included gene therapy and immunotherapy approaches mostly eradicate cancer residuals in breast cancer and reduce the incidence of relapse and GVHS in leukaemia. Furthermore, clinical trials in gene therapy and immunotherapy filed for cancer require more randomization and double-blinding trial design with increased participants number to obtain a definitive outcome.