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Cancer Immunotherapeutics & Tumor Immunology

At City of Hope, we are advancing immunotherapy as an approach to treat and cure devastating illnesses - from conducting innovative research in the laboratory to improving life-saving standard treatments in the clinic. Researchers in the Department of  Cancer Immunotherapeutics & Tumor Immunology are pioneering medical science that harnesses the power of the human immune system and results in more powerful, less toxic cures for patients here and around the world.
 
Immunotherapy, a powerful weapon against cancer because of its potential to exploit the body's natural defenses against infection, has been called the "fourth modality" of cancer treatment by the American Cancer Society. The department’s goal is to make it a highly effective primary treatment option.
 
Currently, T-cell therapy and radioimmunotherapy offer renewed hope to people who have exhausted other treatment options. They are also effective for eliminating microscopic residual disease which can lead to cancer recurrence, even after chemotherapy, radiation therapy and surgery have been successful.

Laboratory Research

Peter Lee, M.D., Chair
Dr. Lee seeks to utilize immunotherapy as a less toxic approach to treating patients diagnosed with breast cancer. While many researchers focus on attacking the cancer cell itself, Dr. Lee aims to target the cancer cell as well as its ‘co-conspirators’ - support cells within the tissue stroma and tumor microenvironment. In order to survive, cancer cells recruit and manipulate these support cells, and as a result, a patient’s immune system is destroyed. Right now, Dr. Lee is studying these ‘co-conspirator’ cells to broaden his understanding of their interactions. By gaining a better understanding of the ways these co-conspirators help feed cancer cells, he may be able to develop therapeutics that target both malignant cells and their supporting cells - thereby, restoring and enhancing the immune function in patients with breast cancer.
 
Stephen J. Forman, M.D., F.A.C.P.
An international expert in leukemia, lymphoma and bone marrow transplantation, Dr. Forman helped build City of Hope’s Hematologic Malignancies Program into one of the largest and most successful programs in the world.
 
Dr. Forman's work also focuses on immune-based therapies for treating malignancies, specifically the potential of augmenting the antitumor response of T cells, the body's immune defense against infection and cancerous cells.
 
Dr. Kortylewski is studying the intracellular processing of CpG-siRNA to identify molecular mechanisms needed to make the silencing of cancer-causing genes more effective. As a part of this effort, Dr. Kortylewski is broadening his understanding of TLR9, the protein responsible for recognizing pathogens and infectious agents like cancer cells, and then, activating the body’s immune cells against those pathogens. In mouse studies, Dr. Kortylewski demonstrated that the TLR9 protein helps the foreign siRNA therapeutic escape endosomes (which are responsible for moving and sorting proteins throughout the body, specifically plasma) and reach cytoplasm. There, the therapeutic silences overexpressed Stat3 proteins. Dr. Kortylewski now seeks to verify whether TLR9 perform the same function for siRNA in human immune- and cancer cells. The results of this investigation will ultimately help improve the Cpg-siRNA therapeutic for clinical use.
 
Dr. Yu’s laboratory was the first to validate Stat3, a critical regulator of tumor cell survival and proliferation, as a molecular target for cancer therapy in animal models. Yu's team also discovered the critical role of Stat3 in tumor angiogenesis and tumor immune evasion.
 
She and her colleagues have devised a novel biologic-based drug called CpG-Stat3 siRNA that strikes a dual blow against cancer. It blocks the growth of tumor cells directly, and activates surrounding immune cells to attack the tumor. This drug takes advantage of two components, which block production of the cancer-promoting and immunosuppressive protein STAT3, and direct the therapy specifically to immune and tumor cells. Importantly, CpG-Stat3 siRNA overcomes the limitations of small molecule drugs, which are difficult to design against proteins such as STAT3 that have no enzymatic activity. It also serves as a unique therapeutic platform, as the siRNA can be designed to block virtually any protein of interest that is important for cancer growth and proliferation. In pre-clinical studies, CpG-Stat3 siRNA effectively stymies growth of aggressive lymphomas and the brain cancer glioma, two deadly cancers with no current viable therapies. A clinical grade CpG-Stat3 siRNA is scheduled to begin production at City of Hope’s facilities this year, and Dr. Yu and her colleagues are poised to take this leading-edge therapeutic strategy to first-in-human clinical trials within two years.
 
Identifying the Connection between Stat3 and Diabetes - It has long been established that obesity is a major cause of type 2 diabetes, due in part to specific cells in fat tissue that promote pathogenic T cells and blunt the activity of insulin. Dr. Yu is exploring the connection between Stat3 and the development of diabetes. In efforts to learn more about this potential link, her lab has used genetically-engineered mice whose T cells lack the Stat3 gene. When these mice became obese through forced consumption of a fatty diet, they showed better glucose tolerance compared with comparably overfed normal mice, as well as a shift in the balance of pathogenic T cells toward regulatory T cells. These intriguing findings suggest that Stat3 is common to both cancer and diabetes and suggest that anti-Stat3 therapies, which have thus far been considered primarily for cancer, might also be effective against type 2 and perhaps type 1 diabetes.         
 

Research Initiatives - Advancing Immunotherapy through Translational Research

City of Hope pioneered immunotherapy with groundbreaking work in bone marrow transplantation. Within our Beckman Research Institute, we also developed the genetic processes for rendering monoclonal antibodies (mAbs) more effective in fighting cancer, processes critical for making products such as Avastin, Erbitux, Herceptin and Rituxan. Poised to maximize our world-class expertise, CITI's focus is on six key areas:
 
  • Radioimmunotherapy: using genetically engineered mAbs to carry radioactive isotopes directly to tumor cells. City of Hope pioneered radioimmunotherapy when researchers developed an antibody recognizing a marker on the surface of cancer cells and used it to target tumors.
     
  • Cellular Immunotherapy: genetically reprogramming immune cells to seek out and destroy specific cancers. We were the first to conduct Food and Drug Adminstration-authorized clinical trials with genetically reprogrammed T cells for lymphoma, neuroblastoma and glioma.
     
  • Molecular Immunotherapy: "designer" proteins that fuse two molecules — one that seeks out the tumor and another that triggers the immune system to attack it. CITI researchers were the first group to apply this technology to lymphoma treatment, with clinical trials beginning in 2006.
     
  • Vaccine Immunotherapy: vaccines targeting the p53 protein that result in elimination of cancers by supercharging the body's immune system. CITI scientists are at the forefront of developing and testing new p53-targeted vaccines against breast, prostate, lung and gastrointestinal cancers.
     
  • Tumor Immunology: studying the mechanisms tumors use to evade the immune system. In one example at City of Hope, researchers hope to target Stat3, a powerful protein found in 60 percent of cancer cells. Stat3 not only has the ability to control cell growth — and as a result, tumor growth — but it also helps cancer cloak itself from immune cells and may even disable the immune system itself.
     
  • Lymphoma (SPORE Grant):  City of Hope has been awarded the Specialized Program of Research Excellence (SPORE) grant by the National Cancer Institute (NCI) for translational research studies for Hodgkin’s and non-Hodgkin’s lymphoma. The Lymphoma SPORE grant brings together a number of investigators across four projects, one of which investigates the use of radioimmunotherapy to specifically seek out and destroy malignant cells.
 

Immunotherapy Milestones

City of Hope is a national leader in cancer immunotherapeutics and tumor immunology research, with an infrastructure unmatched by any other biomedical institution in the United States:
 
City of Hope is a pioneer in cancer radioimmunotherapy, a therapeutic strategy in which radiation is targeted to tumors using monoclonal antibodies. City of Hope received a National Cancer Institute grant to support trials to evaluate radioimmunotherapy of colorectal, breast and lung cancers. The quality of our research in the field of molecularly engineered antibodies is reflected by 11 years of National Cancer Institute (NCI)-supported grants.

City of Hope is the only institution with four FDA-authorized clinical trials using genetically reprogrammed T cells; and the first institution to use re-engineered T cell therapy for lymphoma, malignant brain tumors, and for neuroblastoma in children. Researchers were also able to prototype the zetakine chimeric receptor in human clinical trials, which arms us with a new way to target T cells to cancer cells, and expands potential targets from tens to hundreds.

City of Hope offers more clinical studies than any other facility of our size in the nation, with 30 to 40 percent of our patients enrolled in clinical trials at any one time — the national average is less than 5 percent. . This extensive institutional infrastructure for clinical trials maximizes patient safety and the acquisition of information.

City of Hope received a five-year, $11.5 million Specialized Program of Research Excellence (SPORE) grant from the NCI to fund translational research studies that focus on lymphoma, including an emphasis on immunotherapy.

The largest freestanding biologic production facility in the nation, the Center for Biomedicine & Genetics, allows researchers to bypass pharmaceutical and biotech corporations to speed the development of viral vectors, DNA plasmids, and engineered and customized cellular products for phase I and II clinical trials.

Close collaborations with other centers add value to the advances made at City of Hope and capitalize on sharing expertise and capacity with our academic peers such as Baylor University, Memorial Sloan-Kettering, Mayo Clinic, University of Pennsylvania, Johns Hopkins University and the Fred Hutchinson Cancer Research Center.
 

Cancer Immunotherapeutics & Tumor Immunology Faculty

Cancer Immunotherapeutics & Tumor Immunology

Cancer Immunotherapeutics & Tumor Immunology

At City of Hope, we are advancing immunotherapy as an approach to treat and cure devastating illnesses - from conducting innovative research in the laboratory to improving life-saving standard treatments in the clinic. Researchers in the Department of  Cancer Immunotherapeutics & Tumor Immunology are pioneering medical science that harnesses the power of the human immune system and results in more powerful, less toxic cures for patients here and around the world.
 
Immunotherapy, a powerful weapon against cancer because of its potential to exploit the body's natural defenses against infection, has been called the "fourth modality" of cancer treatment by the American Cancer Society. The department’s goal is to make it a highly effective primary treatment option.
 
Currently, T-cell therapy and radioimmunotherapy offer renewed hope to people who have exhausted other treatment options. They are also effective for eliminating microscopic residual disease which can lead to cancer recurrence, even after chemotherapy, radiation therapy and surgery have been successful.

Laboratory Research

Peter Lee, M.D., Chair
Dr. Lee seeks to utilize immunotherapy as a less toxic approach to treating patients diagnosed with breast cancer. While many researchers focus on attacking the cancer cell itself, Dr. Lee aims to target the cancer cell as well as its ‘co-conspirators’ - support cells within the tissue stroma and tumor microenvironment. In order to survive, cancer cells recruit and manipulate these support cells, and as a result, a patient’s immune system is destroyed. Right now, Dr. Lee is studying these ‘co-conspirator’ cells to broaden his understanding of their interactions. By gaining a better understanding of the ways these co-conspirators help feed cancer cells, he may be able to develop therapeutics that target both malignant cells and their supporting cells - thereby, restoring and enhancing the immune function in patients with breast cancer.
 
Stephen J. Forman, M.D., F.A.C.P.
An international expert in leukemia, lymphoma and bone marrow transplantation, Dr. Forman helped build City of Hope’s Hematologic Malignancies Program into one of the largest and most successful programs in the world.
 
Dr. Forman's work also focuses on immune-based therapies for treating malignancies, specifically the potential of augmenting the antitumor response of T cells, the body's immune defense against infection and cancerous cells.
 
Dr. Kortylewski is studying the intracellular processing of CpG-siRNA to identify molecular mechanisms needed to make the silencing of cancer-causing genes more effective. As a part of this effort, Dr. Kortylewski is broadening his understanding of TLR9, the protein responsible for recognizing pathogens and infectious agents like cancer cells, and then, activating the body’s immune cells against those pathogens. In mouse studies, Dr. Kortylewski demonstrated that the TLR9 protein helps the foreign siRNA therapeutic escape endosomes (which are responsible for moving and sorting proteins throughout the body, specifically plasma) and reach cytoplasm. There, the therapeutic silences overexpressed Stat3 proteins. Dr. Kortylewski now seeks to verify whether TLR9 perform the same function for siRNA in human immune- and cancer cells. The results of this investigation will ultimately help improve the Cpg-siRNA therapeutic for clinical use.
 
Dr. Yu’s laboratory was the first to validate Stat3, a critical regulator of tumor cell survival and proliferation, as a molecular target for cancer therapy in animal models. Yu's team also discovered the critical role of Stat3 in tumor angiogenesis and tumor immune evasion.
 
She and her colleagues have devised a novel biologic-based drug called CpG-Stat3 siRNA that strikes a dual blow against cancer. It blocks the growth of tumor cells directly, and activates surrounding immune cells to attack the tumor. This drug takes advantage of two components, which block production of the cancer-promoting and immunosuppressive protein STAT3, and direct the therapy specifically to immune and tumor cells. Importantly, CpG-Stat3 siRNA overcomes the limitations of small molecule drugs, which are difficult to design against proteins such as STAT3 that have no enzymatic activity. It also serves as a unique therapeutic platform, as the siRNA can be designed to block virtually any protein of interest that is important for cancer growth and proliferation. In pre-clinical studies, CpG-Stat3 siRNA effectively stymies growth of aggressive lymphomas and the brain cancer glioma, two deadly cancers with no current viable therapies. A clinical grade CpG-Stat3 siRNA is scheduled to begin production at City of Hope’s facilities this year, and Dr. Yu and her colleagues are poised to take this leading-edge therapeutic strategy to first-in-human clinical trials within two years.
 
Identifying the Connection between Stat3 and Diabetes - It has long been established that obesity is a major cause of type 2 diabetes, due in part to specific cells in fat tissue that promote pathogenic T cells and blunt the activity of insulin. Dr. Yu is exploring the connection between Stat3 and the development of diabetes. In efforts to learn more about this potential link, her lab has used genetically-engineered mice whose T cells lack the Stat3 gene. When these mice became obese through forced consumption of a fatty diet, they showed better glucose tolerance compared with comparably overfed normal mice, as well as a shift in the balance of pathogenic T cells toward regulatory T cells. These intriguing findings suggest that Stat3 is common to both cancer and diabetes and suggest that anti-Stat3 therapies, which have thus far been considered primarily for cancer, might also be effective against type 2 and perhaps type 1 diabetes.         
 

Research Initiatives

Research Initiatives - Advancing Immunotherapy through Translational Research

City of Hope pioneered immunotherapy with groundbreaking work in bone marrow transplantation. Within our Beckman Research Institute, we also developed the genetic processes for rendering monoclonal antibodies (mAbs) more effective in fighting cancer, processes critical for making products such as Avastin, Erbitux, Herceptin and Rituxan. Poised to maximize our world-class expertise, CITI's focus is on six key areas:
 
  • Radioimmunotherapy: using genetically engineered mAbs to carry radioactive isotopes directly to tumor cells. City of Hope pioneered radioimmunotherapy when researchers developed an antibody recognizing a marker on the surface of cancer cells and used it to target tumors.
     
  • Cellular Immunotherapy: genetically reprogramming immune cells to seek out and destroy specific cancers. We were the first to conduct Food and Drug Adminstration-authorized clinical trials with genetically reprogrammed T cells for lymphoma, neuroblastoma and glioma.
     
  • Molecular Immunotherapy: "designer" proteins that fuse two molecules — one that seeks out the tumor and another that triggers the immune system to attack it. CITI researchers were the first group to apply this technology to lymphoma treatment, with clinical trials beginning in 2006.
     
  • Vaccine Immunotherapy: vaccines targeting the p53 protein that result in elimination of cancers by supercharging the body's immune system. CITI scientists are at the forefront of developing and testing new p53-targeted vaccines against breast, prostate, lung and gastrointestinal cancers.
     
  • Tumor Immunology: studying the mechanisms tumors use to evade the immune system. In one example at City of Hope, researchers hope to target Stat3, a powerful protein found in 60 percent of cancer cells. Stat3 not only has the ability to control cell growth — and as a result, tumor growth — but it also helps cancer cloak itself from immune cells and may even disable the immune system itself.
     
  • Lymphoma (SPORE Grant):  City of Hope has been awarded the Specialized Program of Research Excellence (SPORE) grant by the National Cancer Institute (NCI) for translational research studies for Hodgkin’s and non-Hodgkin’s lymphoma. The Lymphoma SPORE grant brings together a number of investigators across four projects, one of which investigates the use of radioimmunotherapy to specifically seek out and destroy malignant cells.
 

Immunotherapy Milestones

Immunotherapy Milestones

City of Hope is a national leader in cancer immunotherapeutics and tumor immunology research, with an infrastructure unmatched by any other biomedical institution in the United States:
 
City of Hope is a pioneer in cancer radioimmunotherapy, a therapeutic strategy in which radiation is targeted to tumors using monoclonal antibodies. City of Hope received a National Cancer Institute grant to support trials to evaluate radioimmunotherapy of colorectal, breast and lung cancers. The quality of our research in the field of molecularly engineered antibodies is reflected by 11 years of National Cancer Institute (NCI)-supported grants.

City of Hope is the only institution with four FDA-authorized clinical trials using genetically reprogrammed T cells; and the first institution to use re-engineered T cell therapy for lymphoma, malignant brain tumors, and for neuroblastoma in children. Researchers were also able to prototype the zetakine chimeric receptor in human clinical trials, which arms us with a new way to target T cells to cancer cells, and expands potential targets from tens to hundreds.

City of Hope offers more clinical studies than any other facility of our size in the nation, with 30 to 40 percent of our patients enrolled in clinical trials at any one time — the national average is less than 5 percent. . This extensive institutional infrastructure for clinical trials maximizes patient safety and the acquisition of information.

City of Hope received a five-year, $11.5 million Specialized Program of Research Excellence (SPORE) grant from the NCI to fund translational research studies that focus on lymphoma, including an emphasis on immunotherapy.

The largest freestanding biologic production facility in the nation, the Center for Biomedicine & Genetics, allows researchers to bypass pharmaceutical and biotech corporations to speed the development of viral vectors, DNA plasmids, and engineered and customized cellular products for phase I and II clinical trials.

Close collaborations with other centers add value to the advances made at City of Hope and capitalize on sharing expertise and capacity with our academic peers such as Baylor University, Memorial Sloan-Kettering, Mayo Clinic, University of Pennsylvania, Johns Hopkins University and the Fred Hutchinson Cancer Research Center.
 

Faculty

Cancer Immunotherapeutics & Tumor Immunology Faculty

Overview
Beckman Research Institute of City of Hope is responsible for fundamentally expanding the world’s understanding of how biology affects diseases such as cancer, HIV/AIDS and diabetes.
 
 
Research Departments/Divisions

City of Hope is a leader in translational research - integrating basic science, clinical research and patient care.
 

Research Shared Services

City of Hope embodies the spirit of scientific collaboration by sharing services and core facilities with colleagues here and around the world.
 

Our Scientists

Our research laboratories are led by the best and brightest minds in scientific research.
 

City of Hope’s Irell & Manella Graduate School of Biological Sciences equips students with the skills and strategies to transform the future of modern medicine.
Develop new therapies, diagnostics and preventions in the fight against cancer and other life-threatening diseases.
 


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