Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Mar/Apr;23(2):115-124.
doi: 10.1097/PPO.0000000000000257.

Antigen Discovery and Therapeutic Targeting in Hematologic Malignancies

David A Braun  1 , Catherine J Wu
Affiliations
Review

Antigen Discovery and Therapeutic Targeting in Hematologic Malignancies

David A Braun et al. Cancer J. 2017 Mar/Apr.

Abstract

Historically, immune-based therapies have played a leading role in the treatment of hematologic malignancies, with the efficacy of stem cell transplantation largely attributable to donor immunity against malignant cells. As new and more targeted immunotherapies have developed, their role in the treatment of hematologic malignancies is evolving and expanding. Herein, we discuss approaches for antigen discovery and review known and novel tumor antigens in hematologic malignancies. We further explore the role of established and investigational immunotherapies in hematologic malignancies, with a focus on personalization of treatment modalities such as cancer vaccines and adoptive cell therapy. Finally, we identify areas of active investigation and development. Immunotherapy is at an exciting crossroads for the treatment of hematologic malignancies, with further investigation aimed at producing effective, targeted immune therapies that maximize antitumor effects while minimizing toxicity.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST: D.A.B. reports no relevant conflict of interest. C.J.W. is a founder of Neon Therapeutics and a member of its scientific advisory board.

Figures

Figure 1
Figure 1. Evolution in the Methods of Tumor of Antigen Discovery
Historical and contemporary methods for tumor antigen identification, identifying T-cell based (green), serology-based (orange), gene expression based (blue) and biochemical/proteomic-based (purple) approaches.
Figure 2
Figure 2. Examples of Tumor Antigens in Hematologic Malignancies
A selection (not exhaustive) of tumor antigens and cell surface markers in a variety of hematologic malignancies.
Figure 3
Figure 3. Potential sources of Neo-antigens in the Hematologic Malignancies
(A) Solid malignancies responsive to immunotherapies tend to have a higher mutational load, with more missense mutations and insertions/deletions, leading to a high number of neo-antigens. (B) Hematologic malignancies tend to have a lower number of somatic mutations, yet are often still able to generate immune responses. Other possible mechanisms for generating neo-antigens in the setting of low somatic mutation burden are gene fusions and alterations in RNA splicing leading to retain introns. Graph of somatic mutation number adapted from ref. .
Figure 4
Figure 4. Immune based therapies in the Hematologic Malignancies vary in degree of antigen-targeting personalization
Immunotherapeutic strategies for hematologic malignancies can be categorized based on whether they are personalized for an individual patient/tumor (bottoms row), and whether they target antigen(s) are known/specified (right column). In the top left panel, immune checkpoint blockade with an anti-PD-1 antibody is depicted. Typically, tumor cells may express a ligand, PD-L1, which binds PD-1 on T cells and ultimately inhibits T cell effector function. Anti-PD-1 antibodies inhibit this effect, leading to T cell activation and effective tumor cell killing. This strategy is not personalized for an individual patient, and the specific target tumor antigen is not known. In the bottom left panel, whole tumor vaccines are depicted, including lethally irradiated tumor cells engineered to secrete GM-CSF to attract APCs (GVAX, left image), and DC/tumor cell fusions, which also leads to antigen presentation and activation of the native immune system. These strategies require personalized products, but the target tumor antigen is not known. In the top right panel, a variety of monoclonal antibody therapies are depicted, including conventional monoclonal antibody therapy against CD20, antibody-drug conjugate targeted against CD33-expressing cells, and the bispecific T cell engages blinatumomab which transiently cross-links T cells with CD19 expressing ALL cells. These strategies target specific antigens, but are not personalized for the individual patient. In the top right panel, CD19-targeting CAR-T cell therapy (bottom) and neo-antigen therapeutic peptide vaccine (top) strategies are depicted. The therapeutic approaches require personalization for the individual patient/tumor, and are targeted against known tumor antigen(s).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–62. - PubMed
    1. Kolb HJ, Mittermuller J, Clemm C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990;76:2462–5. - PubMed
    1. Collins RH, Jr, Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. 1997;15:433–44. - PubMed
    1. Bachireddy P, Hainz U, Rooney M, et al. Reversal of in situ T-cell exhaustion during effective human antileukemia responses to donor lymphocyte infusion. Blood. 2014;123:1412–21. - PMC - PubMed
    1. Zhang W, Choi J, Zeng W, et al. Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion. Clin Cancer Res. 2010;16:2729–39. - PMC - PubMed

MeSH terms

Substances