"Our mission is all about seeing cancer differently"

Significance

Immunotherapy has revolutionized cancer therapy (1–4), however, a significant fraction of patients fail to respond to therapy and may suffer serious side effects (5). Predicting and monitoring therapeutic efficacy remains an important challenge. Techniques to achieve these goals without multiple biopsies or other invasive methods will be critical. The efficacy of the various forms of immunotherapy is a direct result of changes evoked in the tumor microenvironment (TME) and thus noninvasive monitoring of events occurring in the TME can be used to tackle this issue.

Rarely does a patient present with a single metastasis:  usually there are several lesions. It is not possible to do biopsies, immunohistochemistry and immunostaining on all lesions. Some lesions are not even accessible for biopsies (6, 7). Moreover, many cancers evolve quickly and different lesions may differ substantially from each other. Immuno-PET can provide a whole body scan and provide information for all lesions. In a recent study, where breast cancer patients were imaged with an anti-HER2 agent (89Zr-Trastuzumab PET/CT), some patients were identified who had HER2-positive metastases but whose primary tumor was HER2-negative; these women went on to benefit from trastuzumab (Herceptin) treatment (8). Immuno-PET will thus be a useful adjunct to (if not a replacement for) biopsies and immunostaining.

At Revela Biotech, we have developed a method that allows noninvasive monitoring of the immune responses that can be used to evaluate and predict the response to immunotherapy (9, 10). We can now predict, in the B16 melanoma model, the response to immunotherapy based on differences in distribution of CD8 T cells.

Technology 

We are bringing our patented in vivo cancer imaging technology based on 5+ years of research at the Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, and the Boston Children’s Hospital of Harvard Medical School to help patients worldwide. 

Opportunity

We see tremendous opportunity for impact in the rapidly growing oncology space, where real-time visualization of primary tumors, metastasis, and the patient’s own immune system is needed to direct effective care. 

    Edge 

    Revela was founded by an experienced managerial team based in the Boston area, the world’s capital of biotech innovation, and is recruiting a scientific board from multiple collaborating labs at the forefront of cancer research locally and abroad to extend our core competencies. 

    What We've Achieved

    • Detecting small tumors with <1mm diameter (read more)
    • Detecting inflammation (read more)
    • Detecting graft-vs-host disease (GvHD) in a humanized mouse model (read more)
    • Evaluating and predicting the response to immunotherapy (read more)

    References:

    1.         Baumeister, S. H., Freeman, G. J., Dranoff, G., and Sharpe, A. H. (2016) Coinhibitory Pathways in Immunotherapy for Cancer. Annu. Rev. Immunol.. 34, 539–573

    2.         Vesely, M. D., Kershaw, M. H., Schreiber, R. D., and Smyth, M. J. (2011) Natural innate and adaptive immunity to cancer. Annu. Rev. Immunol.. 29, 235–271

    3.         Holzinger, A., Barden, M., and Abken, H. (2016) The growing world of CAR T cell trials: a systematic review. Cancer Immunol. Immunother. CII. 10.1007/s00262-016-1895-5

    4.         Topalian, S. L., Wolchok, J. D., Chan, T. A., Mellman, I., Palucka, K., Banchereau, J., Rosenberg, S. A., and Dane Wittrup, K. (2015) Immunotherapy: The path to win the war on cancer? Cell. 161, 185–186

    5.         Kourie, H. R., and Klastersky, J. (2016) Immune checkpoint inhibitors side effects and management. Immunotherapy. 8, 799–807

    6.         Lear-Kaul, K. C., Yoon, H.-R., Kleinschmidt-DeMasters, B. K., McGavran, L., and Singh, M. (2003) Her-2/neu status in breast cancer metastases to the central nervous system. Arch. Pathol. Lab. Med.. 127, 1451–1457

    7.         Dijkers, E. C. F., Kosterink, J. G. W., Rademaker, A. P., Perk, L. R., van Dongen, G. A. M. S., Bart, J., de Jong, J. R., de Vries, E. G. E., and Lub-de Hooge, M. N. (2009) Development and characterization of clinical-grade 89Zr-trastuzumab for HER2/neu immunoPET imaging. J. Nucl. Med. Off. Publ. Soc. Nucl. Med.. 50, 974–981

    8.         Ulaner, G. A., Hyman, D. M., Ross, D. S., Corben, A., Chandarlapaty, S., Goldfarb, S., McArthur, H., Erinjeri, J. P., Solomon, S. B., Kolb, H., Lyashchenko, S. K., Lewis, J. S., and Carrasquillo, J. A. (2016) Detection of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer Using 89Zr-Trastuzumab PET/CT. J. Nucl. Med. Off. Publ. Soc. Nucl. Med.. 57, 1523–1528

    9.         Rashidian, M., Keliher, E. J., Bilate, A. M., Duarte, J. N., Wojtkiewicz, G. R., Jacobsen, J. T., Cragnolini, J., Swee, L. K., Victora, G. D., Weissleder, R., and Ploegh, H. L. (2015) Noninvasive imaging of immune responses. Proc. Natl. Acad. Sci. U. S. A.. 112, 6146–6151, PMCID: PMC4434737.

    10.       Rashidian, M., Ingram, J., Dougan, M., Dongre, A., Whang, K., LeGall, C., Cragnolini, J. J., Bierie, B., Gostissa, M., Gorman, J., Grotenbreg, G. M., Bhan, A., Weinberg, R. A., and Ploegh, H. L. (2017) Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells. J. Exp. Med., PMCID: PMC5551571.