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Biomedical subjects

K A Foon

Publications and source records attributed to K A Foon.

At least 55 records · Page 3Linked to original sources
PubMed1995

Preclinical evaluation in nonhuman primates of an anti-idiotypic antibody that mimicks the carcinoembryonic antigen.

We have developed and characterized a murine monoclonal antiidiotype (Id) antibody (Ab2), designated 3H1 (IgG1-k) that mimics human carcinoembryonic antigen (CEA). 3H1 was raised against an anti-CEA monoclonal antibody (mAb) 8019 (Ab1) that recognizes a distinct and specific epitope of the 180,000 MW CEA. 3H1 induced specific anti-CEA immune responses in mice and rabbits. In this preclinical study, cynomolgus monkeys (Macaca fascicularis) were immunized with aluminum hydroxide-precipitated 3H1 and tested for the induction of anti-CEA antibodies. Monkeys were injected with 2 mg of 3H1, intracutaneously, four times biweekly. All monkeys developed specific anti-anti-Id (Ab3) responses that were capable of inhibiting binding of the immunizing 3H1 (Ab2) to 8019 (Ab1) and vice versa. Furthermore, immune sera from monkeys contained Ab3 (Abl') antibody that bound to CEA-positive colon carcinoma cell lines but not to CEA-negative MOLT-4 or melanoma cell lines. Also, the Ab3 reacted with purified CEA and competed with Ab1 (8019) for binding to CEA positive LS174-T cells, suggesting that Ab1 and Ab3 may bind to the same epitope. In addition, affinity-purified Ab3 from monkey sera immunoprecipitated the same 180,000 MW CEA as Ab1 8019 and showed an identical pattern as the Ab1 on colon carcinoma specimens by immunoperoxidase staining. The induction of anti-tumor antibodies in monkeys did not cause any apparent side effects. These data suggest that internal image anti-Id can induce tumor-specific humoral immune responses in nonhuman primates and can serve as potential network antigen for triggering active anti-CEA antibodies in colorectal cancer patients.

Animals↗
PubMed1995

Immune response to the carcinoembryonic antigen in patients treated with an anti-idiotype antibody vaccine.

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; some cases were confirmed by immunoprecipitation of purified CEA. We also demonstrated Ab3 stained both autologous and allogeneic colonic tumors. 7 of 12 patients demonstrated idiotype specific T cell proliferative responses and four also showed T cell proliferation to CEA. Toxicity was limited to local reaction with mild fever and chills. All 12 patients eventually progressed after finishing 4-13 dosages. This is the first report demonstrating that a vaccine therapy is capable of breaking "immune tolerance" to CEA in patients with CEA positive tumors. Future studies will focus on treating patients with minimal residual disease.

Adult↗
PubMed1995

Immune responses in patients with T-cell lymphoma treated with an anti-idiotype antibody mimicking a highly restricted T-cell antigen.

We generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) to a highly restricted T-cell antigen designated glycoprotein (gp) 37 that is found on T-cell malignancies but not on normal cells. gp37 is identified by the murine monoclonal antibody SN2 (Ab1) against which the Ab2 was raised. Each of four patients with T-cell lymphoma predominantly confined to the skin received a minimum of four intracutaneous injections of aluminum hydroxide precipitated anti-idiotype murine monoclonal antibody (1 mg/injection) given every 2 weeks. For responding patients, injections were continued on a monthly basis. All tumors were measured along orthogonal major and minor axes, using a ruler and/or calipers, by the same observer. Tumor sizes were documented photographically. Three of the four patients developed specific idiotypic humoral immune responses, and two of the four patients also demonstrated idiotypic cell-mediated responses. Humoral responses included binding of the patients' sera to the anti-idiotype antibody as well as specific inhibition of binding of the SN2 antibody (Ab1) to the anti-idiotype antibody (Ab2). Anti-anti-idiotypic (Ab3) antibody from one patient's serum bound specifically to the gp37-positive cell line MOLT-4 and also to semipurified gp37 antigen. Cell-mediated responses were demonstrated by specific proliferative response to the aluminum hydroxide precipitated anti-idiotype antibody by patients' peripheral blood mononuclear cells. While three of the four patients had extensive disease and did not have clinical responses, one of the patients who had nine discrete skin tumors and peripheral blood involvement without other detectable disease had virtually complete disappearance of the tumors lasting over 11 months. Our results demonstrate that this particular anti-idiotype antibody can induce humoral and cellular immune responses, and at least in one patient led to a meaningful therapeutic response. Future trials should focus on immunocompetent patients with minimal disease.

Amino Acid Sequence↗
PubMed1993

Genetic relatedness of lymphoid malignancies. Transformation of chronic lymphocytic leukemia as a model.

OBJECTIVE: Studies concerning the genetic relatedness between chronic lymphocytic leukemia and the more aggressive B-cell cancers that develop in about 10% of affected persons were reviewed. These B-cell cancers include large B-cell lymphoma (the Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia, and multiple myeloma. Two possible relations were evaluated: development from the chronic lymphocytic leukemia clone (clonal evolution) and development of a genetically unrelated, independent second cancer. DATA SOURCES: An English-language medical literature search was done using MEDLINE (1982 to 1992) and CANCERLIT (1982 to 1992). An extensive manual search of the literature that included meeting abstracts and reports was also done. Approximately 500 articles, abstracts, and book chapters were identified; 102 were selected for detailed analysis. DATA ANALYSIS: Analysis of genetic relatedness between the two cancers considered concordance for immunoglobulin gene rearrangements, for immunoglobulin isotypes and idiotypes, and for cytogenetic abnormalities. CONCLUSIONS: In the case of large B-cell lymphoma, generally thought to arise from the chronic lymphocytic leukemia clone, approximately one half of the patients had genetically unrelated cancers. In prolymphocytic transformation, all cases studied appeared to evolve from the chronic lymphocytic leukemia clone. The few studies of acute lymphoblastic leukemia and multiple myeloma showed genetic relatedness in some cases and unrelatedness in others. These data indicate that progression to more aggressive B-cell cancers in persons with chronic lymphocytic leukemia can result from either clonal evolution or from an independent transforming event.

Burkitt Lymphoma↗
PubMed1992

Therapy of acute myelogenous leukemia.

Treatment of acute myelogenous leukemia (AML) is divided into remission induction and post-remission therapy. Remission induction is usually with cytarabine and an anthracycline. Daunorubicin is commonly used but recent data suggest idarubicin or mitoxantrone are equally effective, possibly better. High-dose cytarabine has also been used for remission induction but is not proven superior. Post-remission treatment is typically with two or more courses of drugs similar to those used for remission induction. Other studies use non-cross resistant drugs and/or high-dose cytarabine. Although some data favor use of high-dose cytarabine, no approach is clearly superior. There is considerable controversy whether persons in first remission and with an HLA-identical sibling should receive a bone marrow transplant immediately or after relapse. Although transplant results appear superior, especially in persons less than 20 years of age, the most effective strategy may be reserving transplants for persons failing chemotherapy. This strategy also applies to persons receiving autologous transplants or transplants from alternative donors, like HLA-matched related or unrelated persons.

Antineoplastic Agents↗
PubMed1992

Renal cell carcinoma treated with continuous-infusion interleukin-2 with ex vivo-activated killer cells.

High-dose recombinant interleukin-2 (rIL-2) results in tumor responses in patients with metastatic renal cell carcinoma ranging from 9 to 31%. Continuous infusion regimens of rIL-2 may be less toxic and may result in greater in vivo lymphokine-activated killer (LAK) cell production. The current trial used a continuous infusion of rIL-2 with ex vivo LAK cells. These cells were pretreated with phenylalanine methyl ester to remove monocytes to allow cell culture at higher concentrations. Twenty-three patients were entered into the trial. Two patients had complete responses (9%) lasting 15+ and 20+ months. Four patients had partial responses (17%) of 9+, 6+, 3, and 3 months, respectively. One partial responder at 9+ months had only minimal residual retroperitoneal disease that may represent scar tissue. All responders had prior nephrectomies. All but one of the responding patients completed a full cycle of rIL-2 at the highest (starting) dose, 6 x 10(6) U/m2. This rIL-2/LAK regimen appears to be an effective therapy for metastatic renal cell carcinoma.

Adult↗
PubMed1992

Interferon-alpha therapy during pregnancy in chronic myelogenous leukaemia and hairy cell leukaemia.

Interferon-alpha is an effective agent in the treatment of chronic myelogenous leukaemia and hairy cell leukaemia. Because interferon-alpha does not inhibit DNA synthesis, we have used it to treat these diseases during pregnancy. We report here two patients with chronic myelogenous leukaemia and two patients with hairy cell leukaemia managed with interferon-alpha during pregnancy. Interferon-alpha was well tolerated, and the pregnancies proceeded without complications. All four infants were apparently normal at birth, and all four have enjoyed normal growth and development. Interferon-alpha may represent relatively safe therapy during pregnancy, because of its lack of inhibition of DNA synthesis. Nevertheless, recommendations regarding the use of interferon-alpha to treat chronic leukaemias during pregnancy must await further experience with this agent in this setting.

Adult↗
PubMed1992

Clinical significance of monoclonal proteins in chronic lymphocytic leukemia.

Serum monoclonal proteins were found in 36 of 111 (32%) chronic lymphocytic leukemia (CLL) patients studied using high-resolution agarose gel electrophoresis combined with immunofixation. In contrast, using immunoelectrophoresis (IEP) and serum protein electrophoresis (SPEP), monoclonal proteins were found in 20 and 4% of CLL patients, respectively. The presence of a monoclonal protein was associated with a median survival of 63 months compared to 103 months for individuals without a monoclonal spike (p < 0.012). This was independent of clinical stage. The data also suggests that the presence of a monoclonal protein may define a group of patients at greater risk for disease progression in the low and intermediate risk groups. (Rai stages, 0, I, II). Further follow-up will be required to determine if this is statistically significant.

Blood Proteins↗
PubMed1992

Biologic response modifiers: therapeutic approaches to lymphoproliferative diseases.

Some biologic agents have proven effective in the treatment of lymphoproliferative diseases by stimulating host antitumor immunity or by applying active antitumor properties that specifically or nonspecifically effect tumor growth or tumor survival. These agents include interferons, which regulate cell gene expression, structure, and function; interleukin-2, which has several functions related to lymphoproliferation and mediation of lymphoid cell transport; anti-idiotype antibodies, which appear to cause a specific antiproliferative response against the patient's tumor; anti-idiotype vaccines, which produce cyclic complementary binding sites and idiotypes to induce specific immunity to tumors with resultant antitumor activity; radioisotope labeled monoclonal antibodies, which directly deliver tumoricidal doses of radiation to tumors, sparing normal tissue toxicity; and monoclonal antibody-immunotoxin conjugates, which directly deliver tumoricidal doses of radiation to tumors, sparing normal tissue toxicity. Encouraging results have been seen in clinical studies with these agents and much knowledge has been gained regarding the mechanisms involved. These findings dictate ongoing therapy modifications to produce continuing progress in the therapeutic applications of biologic agents in lymphoproliferative disease processes.

Humans↗
PubMed1991

Immune markers in hematologic malignancies.

The precise delineation of biologic traits that distinguish normal hematopoietic cells from their malignant counterparts is of fundamental importance in understanding all aspects of hematologic malignancies. An increasingly sophisticated technologic battery has been utilized to dissect out these differences--primarily utilization of monoclonal antibodies, by immunoperoxidase, immunoalkaline phosphatase and flow cytometric techniques. An even more basic understanding of normal and malignant hematopoietic cells has begun to evolve as molecular biology begins to unravel gene misprogramming by Southern and Northern blot analysis and the polymerase chain reaction. These techniques not only help distinguish a normal cell from a malignant one, but characterize the malignant clone as B-lymphoid, T-lymphoid or myeloid and allow further subcategorization within these broad lineages. These distinctions are vital to the entire spectrum of basic and clinical research involving hematologic malignancies and are assuming an increasingly important role in their diagnosis, prognosis and treatment.

Antibodies, Monoclonal↗