Antibodies are molecules that play a critical role in providing protection against infectious disease. They also are thought to be important for prevention or treatment of cancer. Dr. Sherie Morrison's laboratory has pioneered the development of genetically engineered antibodies for many applications. Presently a major focus of the laboratory is producing antibody fusion proteins for the treatment of malignancy. Type I and type II interferons (IFNs) are cytokines which possess both the ability to directly kill cancer cells and to potentiate the anti-cancer immune response. By genetically fusing IFN to antibodies that recognize tumor-associated antigens it is possible to deliver effective doses of IFN in the absence of systemic toxicity. In preclinical studies, Morrison's lab has found anti-CD20-IFN-alpha-2 to be very effective in treating lymphoma and this molecule is now in phase 1 clinical trials. Ongoing studies are assessing the effects of targeting IFN to different tumors including multiple myeloma and ovarian cancer using antibody fusion proteins which antigens on these malignancies.
Vasuthasawat A, Yoo EM, Trinh KR, Lichtenstein A, Timmerman JM, Morrison SL. Targeted immunotherapy using anti-CD138-interferon alpha fusion proteins and bortezomib results in synergistic protection against multiple myeloma. MAbs. 2016 Oct;8(7):1386-1397. Epub 2016 Jun 30.
Yoo EM, Trinh KR, Tran D, Vasuthasawat A, Zhang J, Hoang B, Lichtenstein A, Morrison SL. Anti-CD138-targeted interferon is a potent therapeutic against multiple myeloma. J Interferon Cytokine Res. 2015 Apr;35(4):281-91. doi: 10.1089/jir.2014.0125. Epub 2014 Oct 29.
Trinh KR, Vasuthasawat A, Steward KK, Yamada RE, Timmerman JM, Morrison SL. Anti-CD20-interferon-beta fusion protein therapy of murine B-cell lymphomas. J Immunother. 2013 Jun;36(5):305-18. doi: 10.1097/CJI.0b013e3182993eb9.
Xuan C, Steward KK, Timmerman JM, Morrison SL. Targeted delivery of interferon-alpha via fusion to anti-CD20 results in potent antitumor activity against B-cell lymphoma. Blood. 2010 Apr 8;115(14):2864-71. doi: 10.1182/blood-2009-10-250555. Epub 2010 Feb 4.
Afshar S, Olafsen T, Wu AM, Morrison SL. Characterization of an engineered human purine nucleoside phosphorylase fused to an anti-her2/neu single chain Fv for use in ADEPT. J Exp Clin Cancer Res. 2009 Dec 3;28:147. doi: 10.1186/1756-9966-28-147.