Cell therapy starting materials sourced from HemaCare are being used to support studies focused on the selective expansion of tumor-specific T cells.
In a recent article,  researchers at a Cambridge, MA biotech company describe their work with a fusion protein designed to specifically activate and expand killer T cells that recognize human papilloma virus associated (HPV+) head and neck cancer cells.
Human papilloma virus (HPV) is a viral infection that can initiate many types of cervical, as well as head-and-neck cancers. The majority of these head-and-neck cancers are driven by a peptide known as HPV16 E7. This peptide plays a critical role in both initiating and maintaining HPV+ cancer, and its genetic sequence is highly conserved in HPV+ cancer patients throughout the world. Currently, the global incidence of these cancers is on the rise.
While HPV-preventative vaccines have no therapeutic effect on established disease, T cell therapy studies have shown promising results against HPV+ cancer. The authors of this study reasoned that that they may be able to fight HPV+ cancer by designing a strategy whereby they utilize a fusion protein to selectively activate and expand T cells targeting HPV16 E7 driven cancer.
To test their theory, the research group developed a platform they named Immuno-STATTM (Selective Targeting and Alteration of T Cells). Immuno-STAT is used to create modular peptides capable of modifying the activity of antigen-specific killer T cells. Immuno-STAT peptides interact with two key regulators of T cell function; one of which is known to activate T cells, and another which induces T cell proliferation.
The key to any successful cell therapy research project lies in reliable access to high-quality starting materials. The Cambridge researchers used healthy donor PBMCs isolated from HemaCare leukopaks to examine the effect their fusion peptide would have on human immune cells. PBMCs were cultured in the presence of a peptide they named CUE-101, which was designed to interact with killer T cells that recognize the highly conserved HPV sequence, HPV16 E7. As the authors hoped, CUE-101 was able to selectively bind, activate, and promote the specific expansion of T cells that recognize the HPV-associated peptide in a tissue culture environment.
Following this success, the group went on to attempt to duplicate their results in vivo, to see whether the peptide would also function within a much more complicated living system. For this portion of the research, the authors used transgenic mice with a humanized immune response. Weekly infusions of the CUE-101 peptide resulted in the expansion of HPV-antigen specific population of T cells. The peptide was well tolerated in the mice, and did not promote expansion of non-HPV responsive T cell populations.
Further testing showed that CUE-101 expanded the populations of HPV-responsive T cells in the tumor, spleen, and blood of HPV-associated tumor bearing mice. Administration of CUE-101 also significantly increased anti-tumor activity.
There is still a good deal of work to be done before this new strategy can be used to treat cancer in humans. Currently, efforts are underway to test the efficacy of this new peptide and others like it in combination with anti-PD1 “checkpoint inhibitor” therapies, which interfere with tumor-induced immune suppression. Ultimately, the authors are confident that this novel cell therapy tool will lead to more successful treatments, not just for HPV-based cancer, but for many different types of cancer.
For more information on HemaCare cell therapy starting materials, please visit our website!
- Quayle s. N., et al. CUE-101, a Novel HPV16 E7-pHLA-IL-2-Fc Fusion Protein, Enhances Tumor Antigen Specific T Cell Activation for the Treatment of HPV16-Driven Malignancies. Clinical Cancer Research, AACR. 2020.