Medical Immunology Commons^™

Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells …

A Melanin-Independent Interaction Between Mc1r And Met Signalling Pathways Is Required For Hgf-Dependent Melanoma, Agnieszka Wolnicka-Głubisz, Faith M. Strickland, Albert Wielgus, Miriam Anver, Glenn Merlino, Edward C. De Fabo, Frances P. Noonan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We …

Paracrine Apoptotic Effect Of P53 Mediated By Tumor Suppressor Par-4, Ravshan Burikhanov, Tripti Shrestha-Bhattarai, Nikhil Hebbar, Shirley Qiu, Yanming Zhao, Gerard P. Zambetti, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53⁻/⁻ or Par-4⁻/⁻ mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 …

Analysis Of The Role Of Astrocyte Elevated Gene-1 In Normal Liver Physiology And In The Onset And Progression Of Hepatocellular Carcinoma, Chadia L. Robertson

Theses and Dissertations

First identified over a decade ago, Astrocyte Elevated Gene-1 (AEG-1) has been studied extensively due to early reports of its overexpression in various cancer cell lines. Research groups all over the globe including our own have since identified AEG-1 overexpression in cancers of diverse lineages including cancers of the liver, colon, skin, prostate, breast, lung, esophagus, neurons and neuronal glia as compared to matched normal tissue. A comprehensive and convincing body of data currently points to AEG-1 as an essential component, critical to the progression and perhaps onset of cancer. AEG-1 is a potent activator of multiple pro-tumorigenic signal transduction …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Phase Ii Evaluation Of Dasatinib In The Treatment Of Recurrent Or Persistent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study., Russell J Schilder, William E Brady, Heather A Lankes, James V Fiorica, Mark S Shahin, Xun C Zhou, Robert S Mannel, Harsh B Pathak, Wei Hu, R Katherine Alpaugh, Anil K Sood, Andrew K Godwin

Department of Medical Oncology Faculty Papers

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome.

METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease …

Cell Membrane And Cytoplasmic Epidermal Growth Factor Receptor Expression In Pancreatic Ductal Adenocarcinoma., Amit Mahipal, Mary J Mcdonald, Agnieszka Witkiewicz, Brian I Carr

Department of Medical Oncology Faculty Papers

The significance of over-expression of epidermal growth factor receptor (EGFR) in pancreatic carcinoma is unclear. In this study, we examined the association between EGFR over-expression (membranous and cytoplasmic), the associated histopathologic features and clinical outcomes in post-resection pancreatic cancer patients. EGFR expression was determined immunohistochemically in 90 patients who underwent resection for pancreatic cancer. Cytoplasmic expression was considered positive if EGFR expression was seen in the cytoplasm in ≥ 10% of cells. Cell membrane staining was scored from 0 to 3+, with 2+ and 3+ being considered as membrane over-expression. Overall survival and progression-free survival were calculated using the Kaplan-Meier …

Phase I Evaluation Of Intravenous Ascorbic Acid In Combination With Gemcitabine And Erlotinib In Patients With Metastatic Pancreatic Cancer., Daniel A. Monti, Md, Edith Mitchell, Anthony J Bazzan, Susan Littman, George Zabrecky, Charles J Yeo, Madhaven V Pillai, Andrew B Newberg, Sandeep Deshmukh, Mark Levine

Department of Medical Oncology Faculty Papers

BACKGROUND: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.

METHODS AND FINDINGS: 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of …

Cell-Free Circulating Mirna Biomarkers In Cancer., Meng-Hsuan Mo, Liang Chen, Yebo Fu, Wendy Wang, Sidney W. Fu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Considerable attention and an enormous amount of resources have been dedicated to cancer biomarker discovery and validation. However, there are still a limited number of useful biomarkers available for clinical use. An ideal biomarker should be easily assayed with minimally invasive medical procedures but possess high sensitivity and specificity. Commonly used circulating biomarkers are proteins in serum, most of which require labor-intensive analysis hindered by low sensitivity in early tumor detection. Since the deregulation of microRNA (miRNA) is associated with cancer development and progression, profiling of circulating miRNAs has been used in a number of studies to identify novel minimally …

Complementary And Integrative Oncology In The Cross-Cultural Region Of The Middle East And South Asia., Eran Ben-Arye, Barrie Cassileth, Peter Heusser, Fatma Afifi, Bashar Saad, Senthamil R Selvan

Department of Medical Oncology Faculty Papers

No abstract provided.

A Meta-Analysis Of Array-Cgh Studies Implicates Antiviral Immunity Pathways In The Development Of Hepatocellular Carcinoma., Xu Guo, Yanna Ba, Xi Ma, Jiaze An, Yukui Shang, Qichao Huang, Hushan Yang, Zhinan Chen, Jinliang Xing

Kimmel Cancer Center Faculty Papers

BACKGROUND: The development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations. Array-based comparative genomic hybridization (array CGH) has been applied to a wide range of tumors including HCCs for the genome-wide high resolution screening of DNA copy number changes. However, the relevant chromosomal variations that play a central role in the development of HCC still are not fully elucidated.

METHODS: In present study, in order to further characterize the copy number alterations (CNAs) important to HCC development, we conducted a meta-analysis of four published independent array-CGH datasets including total 159 samples.

RESULTS: Eighty …

Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya

School of Medicine Faculty Publications

Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release …

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation: A Phase 1/2 Trial Performed With Optimized T-Cell Dosing., Dolores Gross, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg …

Ceacam1 Separates Graft-Versus-Host-Disease From Graft-Versus-Tumor Activity After Experimental Allogeneic Bone Marrow Transplantation., Sydney X Lu, Lucy W Kappel, Anne-Marie Charbonneau-Allard, Renée Atallah, Amanda M Holland, Claire Turbide, Vanessa M Hubbard, Jimmy A Rotolo, Marsinay Smith, David Suh, Christopher King, Uttam K Rao, Nury Yim, Johanne L Bautista, Robert R Jenq, Olaf Penack, Il-Kang Na, Chen Liu, George Murphy, Onder Alpdogan, Richard S Blumberg, Fernando Macian, Kathryn V Holmes, Nicole Beauchemin, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.

METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In …

Tumor-Derived Interleukin-10 As A Prognostic Factor In Stage Iii Patients Undergoing Adjuvant Treatment With An Autologous Melanoma Cell Vaccine., Amit Mahipal, Mizue Terai, David Berd, Inna Chervoneva, Kashyap Patel, Michael Mastrangelo, Takami Sato

Department of Medical Oncology Faculty Papers

OBJECTIVES: Interleukin-10 (IL-10) downregulates T-cell-mediated immune responses. We studied the association between IL-10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients undergoing adjuvant treatment with a vaccine prepared from the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP).

METHODS: Forty-four patients with cutaneous melanoma (29 stage III and 15 stage IV) were prospectively evaluated. Tumor cells were extracted from metastatic deposits for production of DNP-modified autologous melanoma cell vaccine. Small aliquots of the melanoma cell suspensions were separated prior to vaccine processing and cultured overnight for IL-10 production. Based on a blind …

In Vitro Migration Of Cytotoxic T Lymphocyte Derived From A Colon Carcinoma Patient Is Dependent On Ccl2 And Ccr2., Klara Berencsi, Pyapalli Rani, Tianqian Zhang, Laura Gross, Michael Mastrangelo, Neal J Meropol, Dorothee Herlyn, Rajasekharan Somasundaram

Department of Medical Oncology Faculty Papers

BACKGROUND: Infiltration of colorectal carcinomas (CRC) with T-cells has been associated with good prognosis. There are some indications that chemokines could be involved in T-cell infiltration of tumors. Selective modulation of chemokine activity at the tumor site could attract immune cells resulting in tumor growth inhibition. In mouse tumor model systems, gene therapy with chemokines or administration of antibody (Ab)-chemokine fusion proteins have provided potent immune mediated tumor rejection which was mediated by infiltrating T cells at the tumor site. To develop such immunotherapeutic strategies for cancer patients, one must identify chemokines and their receptors involved in T-cell migration toward …

Epidermal Growth Factor Receptor Overexpression In Resected Pancreatic Cancer, Amit Mahipal, Mary J. Mcdonald, Agnieszka Witkiewicz, Brian I. Carr

Department of Medical Oncology Faculty Papers

Conclusions:

Membrane EGFR overexpression is associated with poorer clinical outcomes in patients with pancreatic cancer receiving adjuvant therapy post resection.

Cytoplasmic EGFR overexpression is not associated with clinical outcomes.

The Addition Of Rituximab To Fludarabine And Cyclophosphamide Improves Progression-Free Survival In Patients With Previously Treated Chronic Lymphocytic Leukemia., Amit Mahipal, Mark Weiss

Department of Medical Oncology Faculty Papers

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. There has been considerable progress in understanding the biology and treatment of CLL in last 20 years. The introduction of purine analogs (pentostatin, fludarabine, and cladribine) dramatically increased the response rates compared to alkylating agents. Combination chemoimmunotherapy has further improved the overall frequency of response to over 80% in treatment-naïve and over 60% in relapsed/ refractory disease, respectively.

Immunologic Therapy With Cadi-05 For The Treatment Of Advanced Melanoma, Paul J. Mosca Md, Phd, Suresh G. Nair Md, Susan K. Ayre Rn, Ma, Wenjing Shi Rn, Ms, Sherrine Eid Mph, Shantu Amin Phd, Dhimant Desai Phd, Joseph J. Drabick Md, Facp, Bakulesh M. Khamar Md, Arati Sharma Phd, Svetomir N. Markovic Md, Gavin P. Robertson Phd

Department of Medicine

No abstract provided.

A Stable Explant Culture Of Her2/Neu Invasive Carcinoma Supported By Alpha-Smooth Muscle Actin Expressing Stromal Cells To Evaluate Therapeutic Agents, Marie P. Piechocki

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

To gain a better understanding of the effects of therapeutic agents on the tumor microenvironment in invasive cancers, we developed a co-culture model from an invasive lobular carcinoma. Tumor cells expressing HER2/neu organize in nests surrounded by alpha-Smooth Muscle Actin (α-SMA) expressing tumor stroma to resemble the morphology of an invading tumor. This co-culture, Mammary Adenocarcinoma Model (MAM-1) maintains a 1:1 ratio of HER2/neu positive tumor cells to α-SMA-reactive stromal cells and renews this configuration for over 20 passages in vitro.

Methods

We characterized the cellular elements of the MAM-1 model by microarray analysis, and immunocytochemistry. We developed …

Follicular Dendritic Cell Sarcoma Of Lymph Node - A Rare Entity, Safoorah Khalid, Nausheen Yaqoob, Shahid Pervez

Department of Pathology and Laboratory Medicine

Follicular dendritic cells (FDC) are non-lymphoid, non-phagocytic accessory cells in the immune system that are essential for antigen presentation and germinal center reaction regulation1. These cells are CD21+, CD35+, CD1a- and S100 protein + and they show desmosomes ultrastructurally.

The most commonly involved sites by FDC tumors are lymph nodes but may arise at a variety of extranodal sites including oral cavity, tonsil, gastrointestinal tract and liver. Most studies represent single case reports or case series.

Our patient presented with tumor in the lymph nodes. Histology revealed tumor cells with abundant eosinophilic cytoplasm, hyperchromatic and pleomorphic nuclei, and prominent nucleoli. …

Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin

Department of Medical Oncology Faculty Papers

When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate …

Gitr Activation Induces An Opposite Effect On Alloreactive Cd4(+) And Cd8(+) T Cells In Graft-Versus-Host Disease., Stephanie J Muriglan, Teresa Ramirez-Montagut, Onder Alpdogan, Thomas W Van Huystee, Jeffrey M Eng, Vanessa M Hubbard, Adam A Kochman, Kartono H Tjoe, Carlo Riccardi, Pier Paolo Pandolfi, Shimon Sakaguchi, Alan N Houghton, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) is a member of the tumor necrosis factor receptor (TNFR) family that is expressed at low levels on unstimulated T cells, B cells, and macrophages. Upon activation, CD4(+) and CD8(+) T cells up-regulate GITR expression, whereas immunoregulatory T cells constitutively express high levels of GITR. Here, we show that GITR may regulate alloreactive responses during graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Using a BMT model with major histocompatibility complex class I and class II disparity, we demonstrate that GITR stimulation in vitro and in vivo enhances alloreactive CD8(+)CD25(-) T …

Determination Of The Optimal Form Of A Dna Vaccine To Induce An Effective Immune Response Against A Murine B-Cell Lymphoma, Deepti Aurora

All-Inclusive List of Electronic Theses and Dissertations

Tumor vaccines are a promising alternative to chemotherapy for the treatment of cancer. To be effective and safe, a cancer vaccine should specifically target antigens expressed only on tumor cells. The B-cell tumor-derived Ig receptor may be considered a model tumor antigen for cancer vaccine development. Specifically the immunoglobulin idiotype (ld) encoded by the variable region genes (VH and VL) provides a target antigen. Promising results have been obtained in clinical studies of ld vaccination using ld proteins. However, ld protein is laborious and time-consuming to produce. Gene-based vaccines, on the other hand, are inexpensive and offer ease of manipulation …

Il-7 Enhances Peripheral T Cell Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation., Onder Alpdogan, Stephanie J Muriglan, Jeffrey M Eng, Lucy M Willis, Andrew S Greenberg, Barry J Kappel, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor alpha chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into …

Biochemical And Molecular Characterization Of The Prostate-Specific Membrane Antigen (Psma), John Karl Troyer

Theses and Dissertations in Biomedical Sciences

Prostate cancer is the most common malignancy and the second leading cause of cancer death in males in the United States. Additionally, the number of deaths attributed to prostate cancer is increasing at a rate of approximately 8% a year. Development of new diagnostic and therapy strategies are needed in order to improve the life expectancy of patients with this disease. One tool which may allow for improvements in prostate cancer diagnosis and therapy is the monoclonal antibody (MAb) 7E11-C5.3 which was first described in 1987. Since then, the antigen recognized by MAb 7E11-C5.3 has been named the prostate specific …

Identification Of An Idiotypic Peptide Recognized By Autoantibodies In Human Immunodeficiency Virus-1-Infected Individuals, Q. L. Wang, H.-T. Wang, Edwin Blalock, Sybille Müller, Heinz Köhler

Markey Cancer Center Faculty Publications

Antibodies against HIV-1 proteins in HIV-1-infected individuals share a cross-reactive idiotype defined by the monoclonal antiidiotypic antibody 1F7 (5). Using a computer algorithm based on the molecular recognition theory, regions of inverse hydropathy between the variable sequence of 1F7 and human monoclonal anti-HIV-1 antibodies were identified, which are assumed to be involved in idiotype-antiidiotype contacts. A peptide was designed from the proposed contact in the variable heavy chain framework 3-complementarity determining region 3 (FR3-CDR3) of human antibodies and was synthesized. This peptide is recognized by the antiidiotype 1F7 and inhibits the binding of 1F7 to human anti-HIV-1 antibodies which express …

Immune Response To The Carcinoembryonic Antigen In Patients Treated With An Anti-Idiotype Antibody Vaccine, Kenneth A. Foon, Mala Chakraborty, William J. John, Amanda Sherratt, Heinz Köhler, Malaya Bhattacharya-Chatterjee

Markey Cancer Center Faculty Publications

We have generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) designated 3H1, which mimics a specific epitope on the carcinoembryonic antigen (CEA). Patients with CEA positive tumors are immunologically "tolerant" to CEA. We used 3H1 as a surrogate for CEA for vaccine therapy of 12 patients with advanced colorectal cancer. Each of the patients received a minimum of four intracutaneous injections of aluminum hydroxide precipitated 3H1 at either 1, 2, or 4 mg dosage per injection. 9 of 12 patients demonstrated anti-anti-idiotypic (Ab3) response to 3H1. All nine patients generated specific anti-CEA antibody demonstrated by reactivity with radiolabeled purified CEA; …