The Yi Laboratory has been working on tumor immunology and immunotherapy in multiple myeloma (MM) for 20 years. We were first to demonstrate the existence of idiotype-specific T cells in patients with MM and related disorders and that idiotype-specific cytotoxic T cells could lyse autologous primary myeloma cells. We were first to use patient-derived idiotype proteins to vaccinate MM patientsand demonstrated that idiotype-specific T-cell immunity can be enhanced in patients by repeated vaccine injections. Our current work focuses on identifying and using novel and shared MM antigens, e.g., DKK1 and MM-derived heat shock proteins, as tumor antigens to treat patients.
My group is generating novel monoclonal antibodies (mAbs) to treat patients with MM and other cancers. We discovered that mAbs specific to human b2-microglobulin (b2M) induce programmed death of MM and other hematological tumor cells. These mAbs were also active and therapeutic in vivo in xenograft mouse models. Our goal is to develop these and other mAbs as therapeutic agents to treat patients with MM and other malignancies.
We are also working to better understand the importance of the tumor microenvironment in MM resistance to drug treatment and immunotherapies. We discovered that MM-associated soluble factor C-reactive protein (CRP) and macrophages protect MM cells from chemotherapy-induced apoptosis. Elevated CRP levels and higher numbers of macrophages are present in MM patients, and we are elucidating the mechanisms underlying the protective roles of these factors or cells and identifying and developing novel therapies to target these protective environments.
In other words ...
The Yi Laboratory has been investigating the interaction of the body's immune system with tumors of multiple myeloma (MM) for more than 20 years. Certain T cells in patients with MM and related disorders affect primary myeloma cells. We were first to use proteins from patients to vaccinate patients with MM and to improve their T-cell immunity. We currently are working to identify and use anti-tumor agents, including novel monoclonal antibodies, to treat cancer patients. We are also working to better understand the importance of the tumor and its surroundings ("the tumor microenvironment") to learn what causes cancerous tumors to develop resistance to drug treatment and immunotherapies.
Zheng Y, et al. PSGL-1/selectin and ICAM-1/CD18 interactions are involved in macrophage-induced drug resistance in myeloma. Leukemia 2013;27:702-10.
Lu Y, et al. Th9 cells promote antitumor immune responses in vivo. J Clin Invest 2012;122:4160-71.
Qian J, et al. Active vaccination with Dickkopf-1 induces protective and therapeutic antitumor immunity in murine multiple myeloma. Blood 2012;119:161-9.
Yang J, et al. Human C-reactive protein binds activating Fcγ receptors and protects myeloma tumor cells from apoptosis. Cancer Cell 2007;12:252-65.
Yang J, et al. Targeting β2-microglobulin for induction of tumor apoptosis in human hematological malignancies. Cancer Cell 2006;10:295-307.