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Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
Identification of Antigenic Targets
Hans-Peter Gerber1, Leah V Sibener1, Luke J Lee1
13T Biosciences, 1455 Adams Drive, Menlo Park, CA 94025, USA.
Abstract:
The ideal cancer target antigen (Ag) is expressed at high copy numbers on neoplastic cells, absent on normal tissues, and contributes to the survival of cancer cells. Despite significant investments in the identification of cell surface Ags, there is a paucity of targets that meet such ideal cancer target criteria. Recent clinical trials in patients with cancer treated with immune checkpoint inhibitors (ICIs) indicate that cluster of differentiation (CD)8+ T cells, by means of their T cell receptors (TCRs) recognizing intracellular targets presented as peptides in the context of human leukocyte antigen (peptide-human leukocyte antigen complex; pHLA) molecules on tumor cells, can mediate deep and long-lasting antitumor responses in patients with solid tumors. Therefore, pHLA-target Ags may represent the long sought-after, ideal targets for solid tumor targeting by high-potency oncology compounds.
Insights
Ideal cancer targets are rare. However, intracellular targets presented as peptide-human leukocyte antigen (pHLA) complexes on tumor cells show promise for effective cancer immunotherapy, offering new hope for solid tumor treatments.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- The search for ideal cancer target antigens (Ags) with high tumor specificity and essential roles in cancer survival has yielded limited success.
- Existing cell surface Ags often fail to meet the stringent criteria for effective cancer targeting.
Purpose of the Study:
- To explore the potential of intracellular targets, presented as peptide-human leukocyte antigen (pHLA) complexes, as ideal targets for cancer therapy.
- To evaluate pHLA-target Ags as a promising strategy for solid tumor treatment.
Main Methods:
- Analysis of recent clinical trials involving immune checkpoint inhibitors (ICIs).
- Investigation of cluster of differentiation (CD)8+ T cell responses mediated by T cell receptors (TCRs) recognizing pHLA molecules on tumor cells.
Main Results:
- Immune checkpoint inhibitors demonstrate that CD8+ T cells recognizing intracellular targets via pHLA complexes can induce significant and durable antitumor responses in solid tumors.
- This indicates the therapeutic potential of targeting pHLA molecules.
Conclusions:
- Peptide-human leukocyte antigen (pHLA)-target antigens represent a potentially ideal class of targets for solid tumors.
- These targets may enable the development of highly potent oncology compounds for improved cancer treatment.
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