Table 2.

Comparison of ACT, checkpoint blockade, and combinatorial adoptive T-cell and checkpoint blockade therapy

Adoptive T-cell therapy (ACT)Checkpoint blockadeImpact of combination therapy
EfficacyMost experience and efficacy demonstrated with hematologic malignancies (CD19-expressing tumors)Most experience and efficacy demonstrated with solid tumors (malignant melanoma, RCC, NSCLC)Potential for additive or synergistic antitumor efficacy in tumor types where ACT or checkpoint blockade alone has suboptimal efficacy
ToxicityOn-target/off-tumor effectIrAE: Nonspecific autoreactive T-cell activityRisk of additive toxicity
CRS
Effector cell sourceCAR/TCR:
  • Autologous: (Pre–stem cell transplant: patient-derived T cells; post–stem cell transplant: patient-derived engrafted donor T cells that have been tolerized)

  • Allogeneic third-party T cells: Require HLA matching

  • TIL: Tumor-derived

Recruits patients' own T cells without need for apharesis and ex vivo cell manipulationRequires same T-cell source as would be required in ACT alone (refer to adoptive T-cell therapy)
Relies on patient having endogenous tumor-specific T cellsIn contrast to checkpoint inhibition alone, combination therapy does not rely on patient having endogenous tumor-specific T cells
Need for antigen specificityRequires T-cell specificity to cancer-associated antigen:
  • CARs: Different constructs for different tumor types

  • TILs: Patient specific

Effective across tumor types despite varying antigen expression profileAntigen specificity required for ACT (refer to adoptive T-cell therapy)
ScalabilityComplicated ex vivo cell manipulation:
  • TIL: TIL isolation and expansion

  • CAR: Apharesis, T-cell transduction (retroviral, lentiviral, sleeping beauty, gene editing via CRISPER) and expansion

Off-the-shelfCell manipulation required for ACT preparation (refer to adoptive T-cell therapy)
Time for treatment preparationTime lag introduced to allow for ex vivo cell manipulation and expansionReadily availableTime lag introduced for ACT preparation (refer to adoptive T-cell therapy)

Abbreviations: CRS, cytokine release syndrome; IrAE, immune-related adverse event.