Table 1 Classes of Leukemia Antigens

Tumor-associated antigens (TAAs)

WT-1[25], hTERT[26], PRAME[27], HMMR/Rhamm[28]

- multiple candidates identified- often shared by > 1 malignancy

- present on normal tissue

- self antigens that generate low-avidity T-cells- must be successfully processed and presented by the MHC of the malignant cell

Tumor differentiation antigens

PR1[29], CG1[30], CD33[31]

- more restricted distribution than TAAs

- present on subset of normal cells, which can include hematopoietic stem cells

Cancer testis (CT) antigens

Cyclin-A1[32], NY-ESO-1[33] , MAGE[34]

- frequently restricted to non-essential tissues and tumor

- few identified in leukemia

Minor histocompatibility antigens (mHAs)

HA-1[35], ACC1[36], T4A[37], LB-LY75-IK[38]

- result in high avidity allo T-cells since epitopes are foreign to donor- some are largely restricted to hematopoietic compartment

- Necessitate rescue with mHA-negative stem cells to restore normal hematopoiesis- need for allogeneic TCRs

- must be successfully processed and presented by the MHC

Tumor-specific antigens (neoantigens)

BCR-ABL[39], FLT3-ITD[40], B-cell receptor idiotype[41]

- result in high avidity autologous T-cells- many derive from proteins critical in leukomogenesis

- individual-specific- few identified in leukemia since mutation rate is low

Oncoviral antigens

HTLV-I Tax protein[42]

- generate very high-avidity T-cells

- only relevant to virus-initiated malignancies

Extracellular antigens

CD19 (see CD19 section), Lewis Y[43], CD22[44], ROR1[45]

-MHC-independent- interaction with CAR is high-affinity

- many are present on normal tissues

- require CAR for targeting, which can mediate on-target, off-tumor adverse effects