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Table 2 Summary of hematologic tumor antigens being targeted in clinical trials of ACT

From: Adoptive T-cell therapy for Leukemia

Antigen

HLA-restriction

Hematologic Malignancy†

Immunotherapeutic Potential

CD19

No

ALL, CLL, Lymphoma

1) Common to several lymphoid malignancies

2) Highly potent effectors have been developed

3) Cell surface protein that does not require processing or MHC presentation

4) Anti-leukemia effects must be balanced with toxicity against normal B cells

WT-1

Yes

AML, CML, MDS, ALL

1) Has been studied primarily in myeloid hematologic malignancies, although recent work suggests its potential in lymphoid malignancies[222]

2) Minimal expression in normal tissues

3) Requires intracellular processing and antigen presentation

Lewis Y

No

AML, MM

1) At this time, studies are limited to AML and MM

2) Studies to date have shown moderate potency against malignant cells

3) May be limited by GI toxicity

κ Light Chain

No

CLL, lymphoma, MM

1) Limited to lymphoid malignancies and MM

2) Still in early stages of development, therefore potency is difficult to assess

mHA

Yes

Applicable to all hematologic malignancies

1) Potent immune responses against malignant cells, including stem cells

2) May also trigger GvHD

3) Limited by the frequency of the minor allele in the population

4) Difficult to predict off-target tissue expression

BCR-ABL

Yes

CML

1) Limited studies using ACT to target BCR-ABL in the era of tyrosine kinase inhibitors

2) Mainly useful in CML and possibly Ph+ ALL

  1. †Expression of the antigens has been reported in other hematologic and solid tumor malignancies.