Dr. John Timmerman's laboratory studies immunologic approaches to treating lymphomas and related cancers. The immune system can be taught to recognize tumor-associated protein antigens, and under certain conditions, to kill cancer cells bearing those antigens. Just as the immune system can distinguish pathogens from normal body cells, it can, when properly stimulated, attack malignant cells selectively. The principal effectors of immunity are T-cells, antibodies (produced by B-cells), and innate immune cells (natural killer cells and macrophages). Timmerman's lab is working to devise and test strategies to arm each of these immune effectors to kill malignant lymphoma cells. Approaches aimed at weakening the defenses of lymphoma cells against immunologic attack or other pro-apoptotic stimuli are also under investigation. Timmerman's lab tests these approaches using small animal models, cultured human lymphoma cells and clinical trials.
His recent projects include:
- Targeting toll-like receptors agonists to tumors via linkage to lymphoma-specific monoclonal antibodies.
- Delineating the molecular mechanisms of tumor destruction by toll-like receptor agonists.
- Enhancing tumor antigen vaccine immunogenicity using novel carrier protein conjugation chemistries
- Producing tumor immune evasion of T-cells by expression of programmed death ligand 1 (PD-L1).
- Characterizing novel anti-CD20 antibodies against B-cell lymphomas
- Producing dendritic cell vaccines containing antibody-coated tumor cells.
- Killing tumors by antibody-interferon fusion proteins
- Using Interleukin-21 as a treatment for B-cell lymphomas.
Andorsky DJ, Yamada R, Said JW, Pinkus GS, Betting DJ, Timmerman JM, Yamada RE, Said J. Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res. 2011 Jul 1;17(13):4232-44. Epub 2011 May 3
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. Epub 2010 Feb 4
Ansell SM, Hurvitz SA, Koenig PA, LaPlant BR, Kabat BF, Fernando D, Habermann TM, Inwards DJ, Verma M, Yamada R, Erlichman C, Lowy I, Timmerman JM. Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2009 Oct 15;15(20):6446-53. Epub 2009 Oct 6
Varghese B, Widman A, Do J, Taidi B, Czerwinski DK, Timmerman J, Levy S, Levy R. Generation of CD8+ T cell-mediated immunity against idiotype-negative lymphoma escapees. Blood. 2009 Nov 12;114(20):4477-85. Epub 2009 Sep 17
Betting DJ, Yamada RE, Kafi K, Said J, van Rooijen N, Timmerman JM. Intratumoral but not systemic delivery of CpG oligodeoxynucleotide augments the efficacy of anti-CD20 monoclonal antibody therapy against B cell lymphoma. J Immunother. 2009 Jul-Aug;32(6):622-31.