Cellular adoptive immunotherapy

Current cellular adoptive therapies consist of the ex-vivo expansion of TILs from resected tumors and transferred back to the patients' bodies with support of interleukin -2 (IL–2).

[4][5][6] However, previous clinical trials of TIL therapy on patients with ovarian cancer and renal cell carcinoma have only shown mixed results and modest success respectively.

[2] 2) Achieving full function of T cells and tumor microenvironment (TME) with different immunosuppressive mechanisms is another primary concern.

Cost of single infusions of axicabtagene ciloleucel: US$373,000 Tisagenlecleucel: US$475,000 Chimeric antigen receptor T-cells (CAR-T) are predominantly used in cancer immunotherapy.

And the currently developing mRNA vaccine technology may provide the possibility for in vivo CAR induction in the future.

[9] Acute lymphoblastic leukemia (ALL) Anti-CD19 (CD19 is crucial for B cell lineage, which is overexpressed on leukemic B-cells) is the most commonly used and effective CAR in ALL treatments.

Further suggestions from clinical trials such as controlled CD4+ and CD8+ CAR-T could be potential strategies to investigate factors relevant to the drug efficacy, adverse effects, etc.

[8] Neurological complications Confusion, delirium and occasional seizures and cerebral edema are observed as adverse effects of anti-CD19 CAR-T, which still lack well-explained pathogenesis [3].

[8] CAR-T therapy exhibits distinct specificity compared to other adaptive immunotherapies and traditional cancer treatments such as chemotherapy.

[8] CAR-T kill tumor cells specifically by targeting the tumor-associated antigens to keep the damage to healthy tissue at a minimum level.

Additionally, these engineered T-cells can perform their function independent from HLA - major histocompatibility complex (MHC) presentation.

[11] Natural killer cells belong to the innate immune system, while they perform anti-tumor functions in a very similar mechanism to CD8+ cytotoxic T-cells.

Although retroviral vectors exhibit up to 70% efficiency with the presence of membrane-bound cytokines, it would bring problems such as insertional mutagenesis and reduced NK viability.

Side effects should also be reduced by techniques such as tumor reduction prior to therapy and dose adaptive strategies.

If the mRNA delivery strategy is applied to cellular adoptive therapy, the manufacture of CAR immune cells could be more time-efficient and cost-effective.