Why Is CAR-T Cell Therapy Not a First Line Treatment for Blood Cancers?
Ahmed H Mekkawy, Krishna Pillai, Samina Badar, Javed Akhter, Kevin Ke, Sarah J Valle, David L Morris. The combinations of Bromelain and Acetylcysteine (BromAc) with cytotoxics such as Gemcitabine, 5-Fluorouracil or Oxaliplatin have shown a dramatic reduction in IC50 values in a variety of cancers, including colon cancer, suggesting the possibility of effective treatment without undesired side effects. In the current study, we investigated whether a similar effect is presentusing the colorectal cell line LS174T. Animals after acclimatization were randomized and allocated equally in the groups for the different studies (safety, dose-escalation, and efficacy). Drugs were delivered by the intraperitoneal route and animals were monitored for wellbeing. Separately, an efficacy study was conducted with intraperitoneal drug delivery after intraperitoneal tumor induction. At the termination of the experiment, tumors and other tissues were collected for evaluation. BromAcwas safe when delivered intraperitoneally in a rat model at the concentrations used. Subsequent investigations of these adjuvants in combination with Gemcitabine, Oxaliplatin, and 5-Fluorouracil in mice were also proven to be safe. Preliminary efficacy studies with Oxaliplatin and 5-Fluorouracil on tumor growth (LS174T) were negative. Gemcitabine was assessed with BromAcshowing an almost 71% tumor inhibition compared to controls. Thisstudy indicates that Gemcitabine at 2 mg/kg in combination with BromAc3 mg/300 mg/Kg was effective and safe, supporting its potential for future clinical application.