Cancer biotherapy最新文献

{"title":"Identification of melanoma cell surface antigens immunogenic in mice.","authors":"D Johnston,&nbsp;S el Rouby,&nbsp;J C Bystryn","doi":"10.1089/cbr.1994.9.29","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.29","url":null,"abstract":"<p><p>Active immunization to B16 melanoma cells or vaccines induces anti-melanoma immune responses in syngeneic mice. The immunogenic antigens stimulating immunity to this tumor have not been identified. In this study we detected several B16 melanoma antigens immunogenic in syngeneic mice using as probes antimelanoma antibodies induced by immunization to B16 melanoma vaccines. These antigens were identified by SDS-PAGE and autoradiographic analysis of specific immunoprecipitates. They were cell-surface components with approximate molecular weights of 41, 46, 50, 75, 80, and 104 KD. All these antigens were expressed by syngeneic and xenogeneic melanomas and by some unrelated syngeneic tumors but not by normal syngeneic cells, xenogeneic melanocytes, or by B16 melanoma cells obtained from fresh tumors or grown in defined medium. The antigens were distinct from murine viral antigens expressed by B16 melanoma cells and from components of the culture medium used to grow cells for vaccine production. These results indicate that several B16 melanoma cell-surface antigens are immunogenic in syngeneic mice. Expression of these antigens appears to be related to malignant transformation as they were found on all melanomas studied, and some other cancers, but not on normal cells.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 1","pages":"29-38"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.29","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18811597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The war on cancer: new battle plan needed.","authors":"R K Oldham","doi":"10.1089/cbr.1994.9.289","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.289","url":null,"abstract":"","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"289-90"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18723681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A heavy-chain grafted antibody that recognizes the tumor-associated TAG72 antigen.","authors":"Y Sha,&nbsp;J Xiang","doi":"10.1089/cbr.1994.9.341","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.341","url":null,"abstract":"<p><p>Murine anti-TAG72 antibodies react with more than 85% of human colorectal, gastric and ovarian carcinomas. However, the therapeutic utility of murine antibodies in human is severely restricted by their immunogenicity. The construction of humanized antibodies can potentially circumvent this problem. The latter antibodies can be generated by grafting CDRs from a murine antibody onto human immunoglobulin FRs followed by combining the resultant product with human immunoglobulin constant regions. In this study, we constructed a heavy-chain humanized anti-TAG72 antibody that we designated hmM4. This was achieved by the transplantation of CDRs from the murine VH of the ccM4 antibody into FRs of the human myeloma protein NEWM. The humanized antibody hmM4 retained its binding reactivity for the TAG72 antigen as measured by ELISA and Western blotting analysis respectively. However, it showed considerably less immunoreactivity for the TAG72 antigen than the original chimeric antibody ccM4. These results indicate that the murine anti-TAG72 specificity can be grafted to human immunoglobulin, and that the choice of the human immunoglobulin framework for the grafted antibody may be critical in maintenance of the immunoreactivity.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"341-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18723687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I study of interleukin-2 combined with interferon-alpha and 5-fluorouracil in patients with metastatic renal cell cancer.","authors":"A Sella,&nbsp;R G Kilbourn,&nbsp;I Gray,&nbsp;L Finn,&nbsp;A A Zukiwski,&nbsp;J Ellerhorst,&nbsp;R J Amato,&nbsp;C J Logothetis","doi":"10.1089/cbr.1994.9.103","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.103","url":null,"abstract":"<p><p>Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) each has produced a 15%-20% response in metastatic renal cell cancer. Combining IFN-alpha with either IL-2 or 5-fluorouracil (5-FU) enhanced IFN-alpha activity. We have therefore conducted a Phase I Study combining IL-2, IFN-alpha, and 5-FU. The patients were continuously infused with IL-2 (1-3 x 10(6) u/m2) and 5-FU (600-750 mg/m2) for a 5-day period every 28 days, and IFN-alpha (4-5 x 10(6) u/m2) was injected subcutaneously daily. Lymphokine-activated killer (LAK) and natural killer (NK) cell activity was measured on days 0 and 8. Twenty-one patients received 76 courses. All primary tumors were controlled by surgery (81%) or angioinfarction. Hematologic toxicity was mild; median nadir of platelets was 117 K/microL and of granulocytes was 1.2 K/microL. Dose-limiting toxicity included mucositis, liver damage, and hypotension. No treatment-related death occurred, and only one patient required intensive-care-unit support. Two patients had an objective response, one of which was a complete response. Increased LAK cell and NK cell activity occurred at all IL-2 dose levels. Simultaneous delivery of IL-2, IFN-alpha, and 5-FU is safe and shows antitumor and biologic activity. 5-FU did not appear to suppress IL-2-induced LAK and NK cell activation. Maximum tolerated dose of the three-drug combination is IL-2, 2 x 10(6) u/m2, 5-FU 600 mg/m2, and IFN-alpha, 4 x 10(6) u/m2.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"103-11"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth of tumor derived activated T-cells for the treatment of cancer.","authors":"W M Lewko,&nbsp;R W Good,&nbsp;D Bowman,&nbsp;T L Smith,&nbsp;R K Oldham","doi":"10.1089/cbr.1994.9.211","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.211","url":null,"abstract":"<p><p>This report describes the production of Tumor Derived Activated Cell cultures (TDAC, also called tumor infiltrating lymphocytes) from patient tumor biopsies and our preliminary experience growing these cells to therapeutic levels using artificial capillary bioreactor cultures. TDAC were successfully grown in medium containing Interleukin 2 from 80% of the 113 tumor biopsies tested. There was no significant difference in success (growth to 1 x 10(9) cells) comparing primary and metastatic tumors. Many of the tumors were shipped to the laboratory from distant sites. Success rate did decrease with the length of time for tumor transport. Interleukin 4 was beneficial in the development of 1 of 4 TDAC cultures which did not grow with IL-2 only. Seventy-seven bioreactor cultures were initiated for 31 patients. On the average, 1.9 x 10(9) TDAC were inoculated per bioreactor; 3.3 x 10(10) were harvested in 22 days. Twelve liters of medium were required per 1 x 10(10) TDAC produced. TDAC cultures contained T cells with variable ratios of CD4 to CD8 cells. Secreted granulocyte monocyte colony stimulating factor, interferon gamma and tumor necrosis factor were measured in the bioreactor cartridge conditioned medium. Twenty three patients were evaluated. Partial responses were observed in 4 patients including a dramatic remission of scalp nodules in a patient with renal cancer. Results showed that therapeutic amounts of TDAC cells may be produced in a reasonable and cost effective manner using artificial capillary bioreactor cultures.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 3","pages":"211-24"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18820604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of lymphokine-activated killer (LAK) activity in canine lymphocytes with low dose human recombinant interleukin-2 in vitro.","authors":"S C Helfand,&nbsp;S A Soergel,&nbsp;J F Modiano,&nbsp;J A Hank,&nbsp;P M Sondel","doi":"10.1089/cbr.1994.9.237","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.237","url":null,"abstract":"<p><p>Interleukin-2 (IL-2) is an immunostimulatory cytokine that induces activation of peripheral blood lymphocytes (PBL) which can mediate augmented tumor cytotoxicity. Several regimens using IL-2 as treatment for metastatic melanoma and renal carcinoma have shown measurable tumor responses in 10-20% of human patients. Our overall goals are to determine the efficacy of IL-2 as an adjuvant treatment for canine tumors. In order to evaluate the possibility to extend the use of IL-2 in vivo in the dog, we examined the ability of a clinically relevant (low) dose of human recombinant IL-2 (100 units/ml) to enhance the tumoricidal properties of canine PBL in vitro. This was particularly important considering the need to establish the effects on canine PBL by IL-2 at a dose that is potentially achievable in vivo with acceptable side effects. Our data show, for the first time, the ability to separate canine natural killer (NK) cell activity from lymphokine-activated killer (LAK) cell activity (induced with a low IL-2 dose) mediated by canine PBL against two canine cell lines (CTAC and CML-10) used as targets in 4 vs. 16 hour killing assays. LAK cells generated by stimulation of canine PBL with 100 units/ml of IL-2 for 72 hours, could kill CTAC or CML-10 targets up to 11 or 18 times more efficiently, respectively, than fresh PBL in a 4 hour assay. However, the killing of efficiency of the LAK cells was only 2- to 3-fold greater than that of the fresh PBL in a 16 hour assay. This apparent reduction in the killing efficiency of the LAK cells was mostly due to increased spontaneous NK activity by the fresh PBL after 16 hours in culture; both the LAK cells and the fresh PBL (NK cells) mediated a greater overall cytotoxicity after 16 hours than they did in the 4 hour assays. These results indicate that a low dose of human recombinant IL-2 can augment tumor killing by canine PBL in vitro, and suggest that it may be feasible to examine the potential use of IL-2 as an immunotherapeutic agent in tumor-bearing dogs.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 3","pages":"237-44"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18820606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irreversible, severe congestive cardiomyopathy occurring in association with interferon alpha therapy.","authors":"S Zimmerman,&nbsp;D Adkins,&nbsp;M Graham,&nbsp;P Petruska,&nbsp;C Bowers,&nbsp;D Vrahnos,&nbsp;G Spitzer","doi":"10.1089/cbr.1994.9.291","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.291","url":null,"abstract":"<p><p>Interferon alpha is a biologic agent with demonstrated anti-tumor activity in a variety of hematologic and solid malignancies. Many patients treated with interferon experience acute toxicity manifested as a flu-like syndrome of fever, chills, myalgias, and malaise. However, fatigue, anorexia, bone marrow suppression, nausea, vomiting, dizziness, and confusion may also occur. Cardiotoxicity is a rare complication of interferon therapy that most frequently presents as transient episodes of hypotension and tachycardia, with few significant life-threatening cardiovascular effects reported. A small number of cases of suspected interferon-induced cardiomyopathy, all of which improved after discontinuing interferon, have recently been documented. We report a patient with multiple myeloma who developed severe congestive cardiomyopathy while receiving interferon alpha that did not reverse subsequent to discontinuation of interferon therapy. Although the patient had previously received doxorubicin, the presence on endomyocardial biopsy of a prominent intracellular lipid accumulation within myocytes and only grade 2 anthracycline cardiotoxicity suggested that other or additional factor(s) contributed to the severity of this patient's cardiomyopathy. Etiologies of cardiac dysfunction other than interferon and doxorubicin were excluded. While a direct cause-effect relationship between interferon alpha and irreversible congestive cardiomyopathy cannot be firmly established in this case report, patients who either concurrently or sequentially receive interferon and anthracyclines should be carefully monitored for evidence of cardiac toxicity.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"291-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18723682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of serum tumor necrosis factor-alpha and interleukin-6 activity by liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) in normal cats.","authors":"L E Fox,&nbsp;R R King,&nbsp;F Shi,&nbsp;I D Kurzman,&nbsp;E G MacEwen,&nbsp;P S Kubilis","doi":"10.1089/cbr.1994.9.329","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.329","url":null,"abstract":"<p><p>Tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) are products of activated monocytes/macrophages with anti-tumor activity. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) is a potent monocyte/macrophage activator. Sera from cats after intravenous L-MTP-PE administration showed TNF alpha activity using a WEHI-164 cell cytotoxicity assay and IL-6 activity using an IL-6 dependent mouse 7TD1 hybridoma cell proliferation assay. Serum TNF alpha activity peaked at 2 hours after L-MTP-PE administration. Significant differences from lipid-equivalent controls were observed at 2 and 3 hours (P < 0.05). Neutralization of serum TNF alpha activity was accomplished with serial dilutions of rhTNF alpha monoclonal antibody. Serum IL-6 activity peaked at 3 hours after L-MTP-PE administration. Significant differences from lipid-equivalent controls were observed at 2, 3, and 4 hours (P < 0.05). Neutralization of serum IL-6 activity was not achieved with goat anti-rhIL-6 polyclonal antibody. Intravenous L-MTP-PE, but not lipid-equivalent, induces serum TNF alpha and IL-6 activity in normal cats.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"329-40"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18723686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human anti-mouse antibody response in cancer patients following single low-dose injections of radiolabeled murine monoclonal antibodies.","authors":"R O Dillman,&nbsp;D L Shawler,&nbsp;T J McCallister,&nbsp;S E Halpern","doi":"10.1089/cbr.1994.9.17","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.17","url":null,"abstract":"<p><p>We examined the human anti-mouse antibody (HAMA) response in 61 cancer patients following a single, diagnostic injection of any one of ten 111In conjugated murine monoclonal antibodies. Between 1 and 22 mg of antibody containing 1-5 mCi 111In was administered. The populations studied included 30 patients with colorectal carcinoma (four different antibodies), 22 with malignant melanoma (four antibodies), and nine with prostate cancer (two antibodies). Forty-one percent of the patients developed HAMA within 14 days. Three patients (5%) developed an IgM response, five patients (8%) developed an IgG response, and 17 patients (28%) developed both IgM and IgG. Only 27% of the patients with colon cancer developed HAMA, compared to 55% of the melanoma patients and 56% of the prostate cancer patients. There were no correlations among injected dose, various clinical parameters, and HAMA response. There were variations in the HAMA response to different monoclonal antibodies, but population samples were too small to infer significance. Most of the HAMA responses had a significant proportion of idiotypic or isotypic specificity. Only 1/6 patients who were HAMA negative after the first infusion developed HAMA following subsequent infusions of the same monoclonal antibody. Our data demonstrate that a significant percent of cancer patients develop HAMA following a single, low-dose injection of a radiolabeled monoclonal antibody for diagnostic purposes. This may have important implications for the future therapeutic use of monoclonal antibodies in such patients.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 1","pages":"17-28"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18811596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T/Tn antigen vaccine is effective and safe in preventing recurrence of advanced human breast carcinoma.","authors":"G F Springer,&nbsp;P R Desai,&nbsp;H Tegtmeyer,&nbsp;S C Carlstedt,&nbsp;E F Scanlon","doi":"10.1089/cbr.1994.9.7","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.7","url":null,"abstract":"<p><p>For nearly 20 yrs, we used T/Tn antigen vaccine in safe, specific, effective, long-term intradermal vaccination against recurrence of advanced breast carcinoma. Treatment is ad infinitum. All 18 breast carcinoma patients treated, pTNM Stages IV (6), III (6), and II (6), survived > 5 yrs postoperatively; 10 survived > 10 to > 18 yrs; of the latter, three patients each are Stages III and IV. Five additional 5 yr survivors have not yet reached 10 yrs. The probability that our survival results are due to chance, with NCI \"1991 Standard PDQ Data\" as control, for all three stages taken together is: 5-yr survival: p < 1 x 10(-8); 10-yr survival: p < 1 x 10(-5). There were no untoward side effects. The vaccination area presented as a delayed-type hypersensitivity reaction, but at variance with the PPD reaction, with significant inflammation, increase of helper T lymphocytes and decrease of the T suppressor/cytotoxic cell ratio.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 1","pages":"7-15"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18811601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}