Established in 1972 by Charles Todd, City of Hope’s Department of Immunology & Theranostics began at a time in which immune-based strategies for cancer were in their infancy. For example, there were no T cell subsets and antibodies were all polyclonal. Todd, a chemist by training, was well known for his work on CEA (carcinoembryonic antigen), the best known tumor marker of its time, and his structural approach to immune problems. When monoclonal antibody technology became generally available in 1978, John Shively, Ph.D., in Todd’s lab, produced a Mab to CEA that after genetic engineering and radiolabeling went into City of Hope patients as both an imaging and therapeutic agent.
Today, the Department of Immunology & Theranostics continues to advance this original vision, focusing on basic and applied immunology in cancer and diabetes. The department’s principal investigators conduct fundamental research on topics including the role of CEACAM1 in T cell activation, TH17 cells and their role in controlling inflammation, graft-versus-host disease in allogeneic hematopoietic cell transplantation (HCT), and the role of T lymphocytes in type 1 diabetes. Faculty conduct research on bacterial, viral and fungal infectious diseases, including detection and vaccine development, supported by state-of-the-art facilities in mass spectrometry and NMR. Finally, members of the Immunology and Theranostics department are pursuing immunological approaches to detection and treatment of disease. This includes engineered radiolabeled antibodies for immunoPET imaging and radioimmunotherapy, in preclinical models as well as translation into pilot and phase I clinical trials. Additional innovative therapeutic approaches include bispecific antibodies and immunocytokines.
The unique combination of biological and structural studies at the Department of Immunology & Theranostics, has created a thriving, productive environment and a fruitful collaboration among investigators at City of Hope and at other institutions.
Dr. Shively’s lab specializes in studying the CEA gene family. More specifically, he researches the use of anti-CEA antibodies for tumor imaging and therapy, as well as the role of CEACAM1 in T-cell activation and mammary epithelial cell polarization. Dr. Shively is also exploring the relationships of the immune system and genetics to fibromyalgia.
Markus Kalkum, Ph.D.
. — Employs mass spectrometry and proteomics to develop novel diagnostic assays and vaccines
Dr. Kalkum develops mass spectrometric methods for the quantitative analysis of proteins and other molecules in complex biological samples. He is generating novel biochemical assays for the ultrasensitive detection of functional biomolecules. His goal is to improve the early diagnosis and prevention of emerging and of frequently under-diagnosed diseases, including opportunistic fungal and bacterial He is advancing mycosis vaccine development and is studying immunomodulatory compounds of the gut microbiome. These activities are aimed to protect cancer patients from opportunistic infections, improving cancer treatment outcomes.
Helena Reijonen, Ph.D.
— Understanding immune cell repertoire responsible for destruction of insulin-producing beta cells
Dr. Reijonen's research projects aim at understanding the characteristics of the immune cell repertoire, which is responsible for the destruction of insulin-producing beta cells, and how to regulate this process. The focus of her research is identification of the T lymphocytes relevant for the progression of type 1 diabetes and determining the phenotypic signature of these cells.
The magnitude of an immune response is determined by the ratio of inflammatory vs regulatory T (treg) cells. Because the same pool of naïve T cells can differentiate into inflammatory effector T cells or inhibitory Tregs, generation of immune responses requires promoting the differentiation of inflammatory T cells while reciprocally inhibiting the formation of Tregs. Insufficient inflammatory T responses compromise immunity against pathogens, and overwhelming the Th17 responses can lead to autoimmunity such as multiple sclerosis, diabetes and systematic lupus erythematosus. Research in Dr. Sun’s laboratory is focused on understanding the mechanisms regulating T cell differentiation, and developing targeted therapeutics based on these mechanisms.
Anna Wu, Ph.D.
— Development and translation of radiolabeled antibodies for cancer therapy
Dr. Wu’s research interests include engineered antibodies and proteins for targeting, imaging, and therapeutic applications in cancer and immunology, including the use of SPECT, PET, optical and multimodality approaches. Engineered antibody fragments, such as minibodies and diabodies, have been developed and optimized for immunoPET imaging in preclinical models of cancer and in patients. Recently, immunoPET has been extended to imaging immune responses, particularly in response to cancer immunotherapies. As the co-director of the Center for Theranostics Studies at the City of Hope, she is actively engaged in clinical trials involving investigational use of radiopharmaceuticals for imaging and therapy of cancer.
— Dissecting mechanisms whereby mixed chimerism reverses autoimmunity via allogeneic hematopoietic cell transplantation (HCT)
The Defu Zeng Lab is dissecting the mechanisms whereby mixed chimerism reverses autoimmunity. They are also tracing the origin of beta cell regeneration after reversal of autoimmunity. Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies and hereditary disorders as well as refractory autoimmune diseases. Induction of mixed chimerism via allogeneic HCT is also one of the most reliable approaches for induction of organ transplantation tolerance.