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Updated: Jan 22, 2026
Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications
Published on: November 17, 2015
Intracellular targets as source for cleaner targets for the treatment of solid tumors
Hans-Peter Gerber1, Leah V Sibener1, Luke J Lee1
13T Biosciences, 1455 Adams Drive, Menlo Park, CA 94025, United States.
Abstract:
High-potency oncology compounds such as antibody- drug conjugates, T cell redirecting, and CAR-T cell therapies have provided transformational responses in patients with liquid tumors. However, they delivered only limited benefit to solid tumor patients due to the frequent onset of dose limiting toxicities in normal tissues. Such on-target, off-tumor toxicities are caused by recognition of targets present at low-levels on normal tissues. The apparent imbalance between the rapid development of high-potency therapeutic modalities and the slow progress in identification of cleaner targets is illustrated by the fact that most high-potency compounds currently developed in the clinic target cell surface antigens identified over 20 years ago. Therefore, identification of novel, truly tumor-specific targets is critical for the future success of high-potency oncology compounds in solid tumors. One of the most promising approaches to overcome the limitations of targeting cell surface antigens are intracellular targets. The renewed interest in this class of targets is due to the success of immune checkpoint inhibitors, which mediate their anti-tumor responses by activation of cytotoxic T cells recognizing peptide fragments of intracellular targets presented by human leukocyte antigens (HLAs) on the surface of tumor cells. Importantly, many intracellular targets belong to the class of tumor specific antigens (TSAs), which lack presentation on normal tissues. In this report we review the main classes of tumor specific antigens, including viral, neoantigens and shared self-antigens as well as tumor associated antigens (TAAs) and their relevance for therapeutic targeting of solid tumors by high-potency therapeutic modalities.
Insights
Novel intracellular targets are crucial for advancing high-potency oncology treatments in solid tumors. This approach overcomes toxicities associated with targeting cell surface antigens, improving therapeutic efficacy and patient outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Drug Development
Background:
- High-potency oncology compounds show success in liquid tumors but limited benefit in solid tumors due to dose-limiting toxicities in normal tissues.
- On-target, off-tumor toxicities arise from targeting antigens present at low levels on normal tissues.
- Current therapies often target cell surface antigens identified decades ago, highlighting a need for novel targets.
Purpose of the Study:
- To review tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs) as targets for high-potency oncology compounds in solid tumors.
- To discuss the potential of intracellular targets to overcome limitations of current therapeutic strategies.
- To emphasize the critical need for identifying novel, tumor-specific targets for solid tumor treatment.
Main Methods:
- Review of existing literature on tumor-specific antigens and tumor-associated antigens.
- Analysis of the role of intracellular targets in cancer therapy, particularly in relation to immune checkpoint inhibitors.
- Discussion of different classes of TSAs, including viral antigens, neoantigens, and shared self-antigens.
Main Results:
- Intracellular targets offer a promising alternative to cell surface antigens, potentially reducing on-target, off-tumor toxicities.
- Immune checkpoint inhibitors highlight the potential of targeting intracellular antigens presented via human leukocyte antigens (HLAs).
- Tumor-specific antigens, which are not expressed on normal tissues, are key to developing safer and more effective therapies.
Conclusions:
- Identification of novel, truly tumor-specific targets is essential for the successful application of high-potency oncology compounds in solid tumors.
- Intracellular targets, particularly TSAs, represent a promising avenue for improving the efficacy and safety of cancer therapies.
- Further research into TSAs and TAAs will drive the development of next-generation oncology treatments for solid tumors.
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