Medical Specialties Commons^™

Listeria Monocytogenes As A Vector For Cancer Immunotherapy: Current Understanding And Progress, John C. Flickinger, Ulrich Rodeck, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Listeria monocytogenes, a Gram-positive facultative anaerobic bacterium, is becoming a popular vector for cancer immunotherapy. Indeed, multiple vaccines have been developed utilizing modified Listeria as a tool for generating immune responses against a variety of cancers. Moreover, over a dozen clinical trials testing Listeria cancer vaccines are currently underway, which will help to understand the utility of Listeria vaccines in cancer immunotherapy. This review aims to summarize current views on how Listeria-based vaccines induce potent antitumor immunity and the current state of Listeria-based cancer vaccines in clinical trials. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Unleashing Endogenous Tnf-Alpha As A Cancer Immunotherapeutic., Steven F Josephs, Thomas E Ichim, Stephen M Prince, Santosh Kesari, Francesco M Marincola, Anton Rolando Escobedo, Amir Jafri

Articles, Abstracts, and Reports

Tumor necrosis factor (TNF)-alpha was originally identified in the 1970s as the serum mediator of innate immunity capable of inducing hemorrhagic necrosis in tumors. Today, a wide spectrum of biological activities have been attributed to this molecule, and clinical translation has mainly occurred not in using it to treat cancer, but rather to inhibit its effects to treat autoimmunity. Clinical trials utilizing systemic TNF-alpha administration have resulted in an unacceptable level of toxicities, which blocked its development. In contrast, localized administration of TNF-alpha in the form of isolated limb perfusion have yielded excellent results in soft tissue sarcomas. Here we …

Perspectives In Melanoma: Meeting Report From The Melanoma Bridge (30 November-2 December, 2017, Naples, Italy)., Paolo A Ascierto, Igor Puzanov, Sanjiv S Agarwala, Carlo Bifulco, Gerardo Botti, Corrado Caracò, Gennaro Ciliberto, Michael A Davies, Reinhard Dummer, Soldano Ferrone, Thomas F Gajewski, Claus Garbe, Jason J Luke, Francesco M Marincola, Giuseppe Masucci, Janice M Mehnert, Nicola Mozzillo, Giuseppe Palmieri, Michael A Postow, Stephen P Schoenberger, Ena Wang, Magdalena Thurin

Articles, Abstracts, and Reports

Metastatic melanoma represents a challenging clinical situation and, until relatively recently, there was an absence of effective treatment options. However, in 2011, the advanced melanoma treatment landscape was revolutionised with the approval of the anti-cytotoxic T-lymphocyte-associated protein-4 checkpoint inhibitor ipilimumab and the selective BRAF kinase inhibitor vemurafenib, both of which significantly improved overall survival. Since then, availability of new immunotherapies, especially the anti-programmed death-1 checkpoint inhibitors, as well as other targeted therapies, have further improved outcomes for patients with advanced melanoma. Seven years on from the first approval of these novel therapies, evidence for the use of various immune-based and …

Perspectives In Immunotherapy: Meeting Report From The Immunotherapy Bridge (29-30 November, 2017, Naples, Italy)., Paolo A Ascierto, James Brugarolas, Luigi Buonaguro, Lisa H Butterfield, David Carbone, Bruno Daniele, Robert Ferris, Bernard A Fox, Jérôme Galon, Cesare Gridelli, Howard L Kaufman, Christopher A Klebanoff, Ignacio Melero, Paul Nathan, Chrystal M Paulos, Marco Ruella, Ryan Sullivan, Hassane Zarour, Igor Puzanov

Articles, Abstracts, and Reports

Immunotherapy represents the third important wave in the history of the systemic treatment of cancer after chemotherapy and targeted therapy and is now established as a potent and effective treatment option across several cancer types. The clinical success of anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4, first, and anti-programmed death (PD)-1/PD-ligand (L)1 agents in melanoma and other cancers a few years later, has encouraged increasing focus on the development of other immunotherapies (e.g. monoclonal antibodies with other immune targets, adoptive cell transfer, and vaccines), with over 3000 immuno-oncology trials ongoing, involving hundreds of research institutes across the globe. The potential use of these …

Quantification Of Tumor-Associated Macrophages Following Immunomodulation Therapy In A Murine Allograft Model Of Colorectal Carcinoma, Caroline Spainhour

Biomedical Engineering Undergraduate Honors Theses

Colorectal Carcinoma (CRC) is one of the deadliest cancers in the world, with 150,000 new cases annually in the United States. Traditional treatments include chemotherapy and invasive surgery; however, research has shown that only 25% of patients that undergo traditional treatment have a positive result. Immunotherapy is an emerging form of cancer treatment that utilizes the patients’immune system to fight cancer cells by targeting inflammation, which plays a large role in the proliferation and metastasis of cancer cells.

Tumor-associated macrophages (TAMs) are immune cells that affect the inflammatory microenvironment of tumors. TAMs are M1 in the early stages of tumors, …

Oncolog, Volume 63, Number 03, March 2018, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Local Consolidative Therapy Plus Immunotherapy or Targeted Agents for NSCLC: Clinical trials explore surgery/radiation plus immune checkpoint or tyrosine kinase inhibitors for metastatic non-small cell lung cancer
• INBRIEF: CAR T Cells Elicit Durable Responses in Large B Cell Lymphoma
• Managing Opioid Use in Cancer Patients: Vigilance and interventions ensure patient safety
• Hepatitis C Virus Linked to Head and Neck Cancers: Association of HCV with extrahepatic cancers has implications for HCV testing, treatment
• HOUSE CALL: Understanding cancer Risk and Risk factors-Your risk factors might affect your need for cancer screening

Amyloid-Beta Solubility In The Treatment Of Alzheimer's Disease, Michael Paul Murphy

Molecular and Cellular Biochemistry Faculty Publications

No abstract provided.

Bi-Specific And Tri-Specific Antibodies- The Next Big Thing In Solid Tumor Therapeutics, K. Runcie, D. R. Budman, V. John, N. Seetharamu

Journal Articles

No abstract provided.

Oncolog, Volume 63, Number 01, January 2018, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Immunotherapy for Genitourinary Cancers: Clinical trials explore immune checkpoint inhibitors for bladder, kidney, prostate cancers
• Active Surveillance for Ductal Carcinoma in Situ: COMET trial compares frequent mammography to standard treatment with surgery
• Radiation Plus Chemotherapy for Nasal NK T Cell Lymphoma: Clinical trial may standardize treatment for rare cancer
• HOUSE CALL: Mammography Is Essential for Breast cancer Screening- FDA warns against clinics that advertise screening without mammography
• USEFULRESOURCES: Videoconferences Allow Collaboration in Cancer Prevention, Treatment, Survivorship

Allergen Specific Immunotherapy And The Effect On Allergy Induced Asthma, Cord Tanner Landrum

Physician Assistant Scholarly Project Papers

Allergies are a major public health problem affecting over 300 million people worldwide (Asamoah et. al). An allergic response can occur when a harmless substance, such as tree pollen, is inhaled into the body and mistakenly identified as a harmful substance. Antibodies then bind to the allergen causing a release of chemicals that leads to symptoms such as nasal congestion, runny nose, itchy eyes or skin reactions. For some people, this reaction can also affect the lungs and airways leading to asthma symptoms.

This review analyzes articles from PubMed, Cochran, Clinical Key and references found from UpToDate articles to assess …

Memory Potential, Molecular Characterization, And Translational Applications Of The Novel Theo/Tceo T Cell Phenotype, Todd Bartkowiak, Todd Bartkowiak

Dissertations and Theses (Open Access)

T cells comprise a substantial arm of the immune system and are exquisitely adapted to combat pathogens and tumors. The inflammatory environment largely dictates the nature of T cell response. A hallmark of T cell-mediated immunity is formation of immunological memory; the ability to respond more potently to re-encounter with pathogens. The immune system is also capable of recognizing tumors as foreign, much like viral or bacterial pathogens. Tumors have evolved, though, to generate an immunosuppressive environment to avoid destruction. The field of immunotherapy seeks to overcome immune suppression, in part by targeting T cell co-receptors on the cell surface …

Dynamic Assessment Of Nk Cell Interactions With Pediatric Tumor Cells To Predict Response To Immunotherapy, Arianexys Aquino Lopez

Dissertations and Theses (Open Access)

Due to Natural Killer (NK) cells’ capacity to target tumor cells without prior sensitization, adoptive NK cell therapy represents a promising immunotherapy approach for pediatric cancer patients. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion. Given that NK cells are heterogeneous, with variable receptor expression and potential to target tumor cells, the purpose of my study was to determine whether subpopulations of NK cells with enhanced anti-tumor potential could be identified for increased potency of the NK cell infusion product. In addition, we previously showed that our expanded NK …

The Need For A Network To Establish And Validate Predictive Biomarkers In Cancer Immunotherapy., Giuseppe V Masucci, Alessandra Cesano, Alexander Eggermont, Bernard A Fox, Ena Wang, Francesco M Marincola, Gennaro Ciliberto, Kevin Dobbin, Igor Puzanov, Janis Taube, Jennifer Wargo, Lisa H Butterfield, Lisa Villabona, Magdalena Thurin, Michael A Postow, Paul M Sondel, Sandra Demaria, Sanjiv Agarwala, Paolo A Ascierto

Articles, Abstracts, and Reports

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, the entire medical oncology field has been revolutionized by the introduction of immune checkpoints inhibitors. Despite success in a variety of malignancies, responses typically only occur in a small percentage of patients for any given histology or treatment regimen. There are also concerns that immunotherapies are associated with immune-related toxicity as well as high costs. As such, identifying biomarkers to determine which patients are likely to derive clinical benefit from which immunotherapy and/or be susceptible to adverse side effects is a compelling clinical and …

Tumor And Microenvironment Evolution During Immunotherapy With Nivolumab., Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan

Articles, Abstracts, and Reports

The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific …

Timing Of Pd-1 Blockade Is Critical To Effective Combination Immunotherapy With Anti-Ox40., David J Messenheimer, Shawn M. Jensen, Michael E Afentoulis, Keith W Wegman, Zipei Feng, David J Friedman, Michael J. Gough, Walter Urba, Bernard A Fox

Articles, Abstracts, and Reports

Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 …

The Heat-Stable Enterotoxin Receptor, Guanylyl Cyclase C, As A Pharmacological Target In Colorectal Cancer Immunotherapy: A Bench-To-Bedside Current Report., Trevor R. Baybutt, Allison A. Aka, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Cancer immunotherapy is becoming a routine treatment modality in the oncology clinic, in spite of the fact that it is a relatively nascent field. The challenge in developing effective immunotherapeutics is the identification of target molecules that promote anti-tumor efficacy across the patient population while sparing healthy tissue from damaging autoimmunity. The intestinally restricted receptor guanylyl cyclase C (GUCY2C) is a target that has been investigated for the treatment of colorectal cancer and numerous animal, and clinical studies have demonstrated both efficacy and safety. Here, we describe the current state of GUCY2C-directed cancer immunotherapy and the future directions of this …

Emerging Therapies For Stage Iii Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy And Immunotherapy, Sameera S. Kumar, Kristin A. Higgins, Ronald C. Mcgarry

Radiation Medicine Faculty Publications

The current standard of care for locally advanced non-small cell lung cancer (NSCLC) includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT) has shown …

Oncolog, Volume 62, Number 09, September 2017, Joe Munch, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Laser Interstitial Thermal Therapy for Spinal Metastases: Laser technique may be alternative to open surgery prior to stereotactic radiation therapy for metastases adjacent to the spinal cord.
• Immunotherapy Plus Targeted Therapy for Anaplastic Thyroid Cancer: Trial combines atezolizumab with targeted or cytotoxic agents for patients with anaplastic or poorly differentiated thyroid cancer.
• A New era in Follicular Lymphoma: Newly approved drugs, clinical trials represent shift from cytotoxic to targeted and immunotherapeutic agents.
• HOUSE CALL: Understanding Clinical Trials- Trials provide access to new cancer treatments
• INBRIEF: Repeat Surgery for Close Margins May Be Unnecessary for DCIS Patients Receiving Radiation Therapy

Improving Nk Cell Therapy For Osteosarcoma, Jennifer Foltz

Dissertations and Theses (Open Access)

Osteosarcoma (OS) is the most common primary bone tumor. Despite new treatment options, 5-year survival for metastatic OS has remained at only 30% for the last 30 years. Adoptive transfer of Natural Killer (NK) cells holds promise for a new, non-toxic therapy for OS. NK cells are part of the innate immune system and readily kill metastatic and chemotherapy-resistant OS in vitro and in murine models. However, there is little data regarding their efficacy in animal models with an intact immune system. In addition, the OS tumor microenvironment is highly suppressive, producing TGFβ which impedes NK cell killing of solid …

Oncolog, Volume 62, Number 07, July 2017, Joe Munch, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• RAS Mutations and Colorectal Cancer Liver Metastases: Gene mutations may have implications for local therapy for liver metastases from colorectal cancer.
• Active Surveillance for Prostate Cancer: Clinical trial may clarify which patients with prostate cancer will benefit from active surveillance rather than immediate treatment.
• Gut Microbiome May Affect Immunotherapy Response in Melanoma: Metastatic melanoma patients who experience responses to checkpoint inhibitors have a distinct gut bacterial genetic signature.
• HOUSE CALL: Cancer-Related fatigue-Tips for fighting fatigue

Chemical Modulation Of Cancer Cells To Enhance Tumor Immunity, Florisela Herrejon Chavez

PSU McNair Scholars Online Journal

Breakthroughs in immunotherapy have led to cancer therapeutics that activate the immune system by blocking inhibitory mechanisms. This class of therapeutics has resulted in longer survival rates for cancer patients, some living over 10 years after being diagnosed as terminally ill. However, only a small fraction of patients who receive immunotherapy drugs respond favorably.Recent studies suggest that certain anticancer agents (both cytotoxic chemotherapeutics and targeted drugs) stimulate immune recognition of cancers. Identification of such immunomodulatory anticancer agents would make ideal partners for current immunotherapy treatments, thus increasing the proportion of the treated patients who benefit from immunotherapy. This study aimed …

Oncolog, Volume 62, Number 05-06, May - June 2017, Joe Munch, Bryan Tutt, Kathryn Hale

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Chimeric Antigen Receptor-Directed Natural Killer Cells for B Cell Malignancies: New take on an experimental therapy holds promise for patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia, other lymphoid cancers.
• Preoperative Exercise Program for Pancreatic Cancer Patients: Prehabilitation regimen to improve functional status during chemotherapy evaluated in clinical trials.
• Neoadjuvant Immunotherapy for Non-Small Cell Lung Cancer: Clinical Trial will evaluate immune checkpoint inhibitors in patients with operable early-stage disease.
• HOUSE CALL: Genetic Screening for Hereditary Cancer Syndromes: Genetic counseling, testing help people assess, manage cancer risk

Induction And Characterization Of Anti-Tumor Endothelium Immunity Elicited By Vallovax Therapeutic Cancer Vaccine., Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari

Articles, Abstracts, and Reports

ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium. Using defined antigens associated with tumor endothelial cells, specific molecular entities were identified as being targeted by ValloVax induced antibodies. Binding of predominantly IgG …

Role Of Modern Immunotherapy In Gastrointestinal Malignancies: A Review Of Current Clinical Progress, Zin W. Myint, Gaurav Goel

Markey Cancer Center Faculty Publications

Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms. Immune checkpoint blockade with antibodies directed against these pathways has already shown clinical efficacy that has led to their FDA approval in the treatment of …

Immunotherapy Of Head And Neck Cancer: Emerging Clinical Trials From A National Cancer Institute Head And Neck Cancer Steering Committee Planning Meeting., Julie E Bauman, Ezra Cohen, Robert L Ferris, David J Adelstein, David M Brizel, John A Ridge, Brian O'Sullivan, Barbara A Burtness, Lisa H Butterfield, William E Carson, Mary L Disis, Bernard A Fox, Thomas F Gajewski, Maura L Gillison, James W Hodge, Quynh-Thu Le, David Raben, Scott E Strome, Jean Lynn, Shakun Malik

Articles, Abstracts, and Reports

Recent advances have permitted successful therapeutic targeting of the immune system in head and neck squamous cell carcinoma (HNSCC). These new immunotherapeutic targets and agents are being rapidly adopted by the oncologic community and hold considerable promise. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issue of how to further investigate the use of immunotherapy in patients with HNSCC. The goals of the meeting were to consider phase 2 or 3 trial designs primarily in 3 different patient populations: those with previously untreated, human papillomavirus-initiated oropharyngeal cancers; those with previously untreated, human papillomavirus-negative HNSCC; and …

Oncolog, Volume 62, Number 04, April 2017, Bryan Tutt, Sarah Bronson

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Advances in Surgical Management of Lymphedema: New options reduce edema in limbs, improve quality of life for cancer patients with lymphedema.
• Noncytotoxic First-Line Therapy for Mantle Cell Lymphoma: First-line therapy with targeted and immunotherapy agents produces high response rates in mantle cell lymphoma.
• Reports from the Survivorship Research Symposium: Research on BK virus, heart failure, and aspiration in cancer survivors.
• HOUSE CALL: Types of Immunotherapy for Cancer: Understanding different approaches to immunotherapy

Immunotherapy Biomarkers 2016: Overcoming The Barriers., James L Gulley, Jay A Berzofsky, Marcus O Butler, Alessandra Cesano, Bernard A Fox, Sacha Gnjatic, Sylvia Janetzki, Shyam Kalavar, Vaios Karanikas, Samir N Khleif, Ilan Kirsch, Peter P Lee, Cristina Maccalli, Holden Maecker, Jeffrey Schlom, Barbara Seliger, Janet Siebert, David F Stroncek, Magdalena Thurin, Jianda Yuan, Lisa H Butterfield

Articles, Abstracts, and Reports

This report summarizes the symposium, 'Immunotherapy Biomarkers 2016: Overcoming the Barriers', which was held on April 1, 2016 at the National Institutes of Health in Bethesda, Maryland. The symposium, cosponsored by the Society for Immunotherapy of Cancer (SITC) and the National Cancer Institute (NCI), focused on emerging immunotherapy biomarkers, new technologies, current hurdles to further progress, and recommendations for advancing the field of biomarker development.

Oncolog, Volume 62, Number 03, March 2017, Bryan Tutt, Joe Munch, Brandon C. Strubberg

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Immunotherapy for Glioblastoma: Clinical trials test innovative immunotherapy approaches against brain tumors.
• Virus-Specific T Cells Treat Posttransplant Infections: Banked T cells offer "off-the-shelf" therapy for patients with BK virus, JC virus, Cytomegalovirus infections after stem cell transplant.
• Intensity-Modulated Proton Therapy for Oropharyngeal Cancer: Clinical trial compares outcomes of intensity-modulated proton therapy, standard radiation therapy.
• HOUSE CALL: Lung Cancer Screening-Low-dose computed tomography can detect lung cancer early

Impact Of Sequencing Targeted Therapies With High-Dose Interleukin-2 Immunotherapy: An Analysis Of Outcome And Survival Of Patients With Metastatic Renal Cell Carcinoma From An On-Going Observational Il-2 Clinical Trial: Proclaim, Joseph I Clark, Michael K K Wong, Howard L Kaufman, Gregory A Daniels, Michael A Morse, David F Mcdermott, Sanjiv S Agarwala, Lionel D Lewis, John H Stewart, Ulka Vaishampayan, Brendan Curti, René Gonzalez, Jose Lutzky, Venkatesh Rudraptna, Lee D Cranmer, Joanne M Jeter, Ralph J Hauke, Gerald Miletello, Mohammed M Milhem, Asim Amin, John M Richart, Mayer Fishman, Sigrun Hallmeyer, Sapna P Patel, Peter Van Veldhuizen, Neeraj Agarwal, Bret Taback, Jonathan S Treisman, Marc S Ernstoff, Jessica C Perritt, Hong Hua, Tharak B Rao, Janice P Dutcher, Sandra Aung

Articles, Abstracts, and Reports

BACKGROUND: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2).

PATIENTS AND METHODS: Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in Proleukin

RESULTS: Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an …

Differential Phenotypes Of Memory Cd4 And Cd8 T Cells In The Spleen And Peripheral Tissues Following Immunostimulatory Therapy., Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka R Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy

Articles, Abstracts, and Reports

BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative …