Table 1 The major advantages and disadvantages of various methods of generating T cells for the purpose of adoptive transfer
From: Adoptive cell transfer: new perspective treatment in veterinary oncology
Therapy type | Advantages | Disadvantages |
|---|---|---|
Tumor-infiltrating lymphocytes (TILs) | Recognize tumor-specific antigens | Isolation difficulties—not applicable for all of the cancer types |
High objective response against cancer reaching even up to 70% | Labor and time consuming | |
Sustained remission | Not applicable for larger group of patients | |
Low recurrence rate | Not all of the TILs are reactive to tumor antigens | |
| Â | Presence of tumor-reactive T cells is indispensable | |
TCR-engineered lymphocytes | Does not require presence of tumor antigen-specific T cells | Competition between transgenic TCR and endogenous TCR |
Lymphocytes can be obtained from blood not from tumor tissue | Heterodimer formation and possibility of gaining unknown antigen-specificity | |
| Â | Expression of two distinct TCR was associated with autoimmunity | |
Chimeric antigen receptor (CAR)—engineered T lymphocytes | Specific for broad-range of antigens including non-proteinaceous Ag | Fusion of various signaling domains may alter proper signaling cascade |
MHC-independent antigen recognition | CAR expression may not be stable | |
Suitable for a relatively wide range of patients—not HLA-restricted | Uncertainties regarding the type of signaling domains and their order for proper T cell function | |
Production of large quantities in relatively short time | Antigen specificity must be selected with caution | |
Putative improvement of T cell properties such as proliferation, activation or cytokine secretion by insertion of specially designed CAR | May cause toxicity (on target/off tumor effect) | |
| Â | CAR biology and interaction with different cancer types and TME not well defined yet | |
| Â | Identification of optimal CAR still based on experimental procedures | |
Genome editing technologies (ZFN, TALENS, CRISPR/Cas) | Enhancement of T cells biology (e.g. resistance to TMI, cytokine secretion) | Possible off-target effect |
Applicable for wide-range of dysfunctions | Technical problems with delivery and efficiency | |
Allow to overcome limitations of TCR-engineered and CAR T cells (elimination of endogenous TCR expression) | May induce immune response against bacterial components of GE technology | |
Applicable for greater number of patients | Controversial, ethical issues |