Figure 2.

Types of telomerase-targeted cancer immunotherapies. (I) Peptide vaccines—single or multiple hTERT antigen peptides with different fragments are injected into the human body and recognized by APCs, which subsequently activate T and B cells. (II) DNA vaccines—plasmids carrying hTERT DNA with special epitopes are usually electroporated to sensitize APCs, which process and present antigens to activate T and B cells. (III) hTERT-targeting DCs—DCs are isolated from patient blood, hTERT antigen peptides are used to stimulate the DCs in vitro, and the synthetic vaccine is injected back into the patient to activate T and B cells. (IV) ACT therapies—leukapheresis, performing using apheresis equipment to separate leukocytes from peripheral blood, at the same time returning autologous plasma, platelets and erythrocytes to the patient, is utilized to activate autologous lymphocytes and induce their proliferation in vitro, and expanded cells are then reinfused into the patient to directly kill cancer cells; ACT mainly includes TILs, TCR-T cells, CAR-T cells, and BiTE therapy. TILs directly perform functions and expand. TLI therapy was developed to introduce and integrate part of a TAA gene into patients’ isolated lymphocytes, and then these cells were reinfused into the patients to trigger a targeted immune response. TCR-T-cell therapy involves the integration of the hTERT gene into a TCR sequence and subsequent transfection into T cells, which can then express the TCR that specifically recognizes hTERT. CAR-T-cell therapy involves the combination of an hTERT antigen fragment with T-cell surface molecular signals (CD3, etc.) for subsequent transfection into T cells, which can express the CAR. BiTE therapy involves the combination of a single-chain antibody specific for a T-cell surface molecule with a single-chain antibody specific for a tumor cell surface antigen; the antibody chains are linked to form an hTERT-specific BiTE, and transfected T cells can target, bind, and kill tumor cells. (V) Antibody therapy—direct injection of anti-hTERT antibodies. (VI) hTERT mRNA may be introduced into the human body and after being engulfed by the APC, it is directly translated into the hTERT protein to induce an immune response. But we should pay some attention to underlying side effects. DC, dendritic cell; hTERT, human telomerase reverse transcriptase; phTERT, a synthetic highly optimized full-length hTERT DNA vaccine; APC, antigen-presenting cell; TIL, tumor-infiltrating lymphocyte; TLI, transgenic lymphocyte immunization; TCR-T, T-cell receptor-engineered T; CAR-T, chimeric antigen receptor T; BiTE, bispecific T-cell engager; TAA, tumor-associated antigen; CAR, chimeric antigen receptor.