International journal of cancer. Supplement = Journal international du cancer. Supplement最新文献_第4页

Role of adhesion molecules in the immune reaction to M-MSV-induced tumors. 黏附分子在m - msv诱导肿瘤免疫反应中的作用。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

A Rosato, V Bronte, S Mandruzzato, A Zambon, F Calderazzo, G Biasi, P Zanovello, D Collavo

{"title":"Role of adhesion molecules in the immune reaction to M-MSV-induced tumors.","authors":"A Rosato, V Bronte, S Mandruzzato, A Zambon, F Calderazzo, G Biasi, P Zanovello, D Collavo","doi":"","DOIUrl":"","url":null,"abstract":"We have investigated the in vivo role of 2 different adhesion molecules, LFA-1 and LECAM-1, in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)-induced tumors, which undergo a peculiar spontaneous regression due to generation of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated administration of anti-LFA-1 monoclonal antibody (FD441.8 MAb), i.p. or at the site of virus inoculation, enhanced tumor growth and delayed regression, while i.p. administration of anti-LECAM-1 MEL-14 MAb gave rise to tumors that grew progressively and caused host death. Evaluation of the immunological response in MAb-treated mice showed reduced generation of virus-specific CTL precursors (p) in the spleen of animals given FD441.8 MAb i.p.; CTLp frequency in locally treated mice overlapped with that of control mice injected with virus only. FD441.8 MAb treatment did not interfere with CTL homing in the tumor, since the frequency of M-MSV-specific CTLps in sarcomas was similar in treated and control mice. Cytofluorimetric analysis indicated that the majority of tumor-infiltrating lymphocytes (TIL) from MAb-treated mice were covered by anti-LFA-1 MAb, and lacked cytotoxic activity when assayed against target cells bearing relevant tumor antigens. Instead, in mice injected i.p. with MEL-14 MAb, a very low frequency of CTLps was detected in lymph nodes draining the tumor area, and within the tumor. Our results indicate that enhanced tumor growth, depending on the MAb used, is the resultant of an inhibitory effect on different T-lymphocyte functions. Tumor progression in anti-LFA-1 MAb-injected mice is explained mostly by blockage of CTL lytic activity at the tumor site; in mice receiving i.p. MEL-14 MAb treatment, by the failure of naive T lymphocytes to enter peripheral lymph nodes and subsequently by the lack of generation of tumor-specific CTLs.","PeriodicalId":77178,"journal":{"name":"International journal of cancer. Supplement = Journal international du cancer. Supplement","volume":"7 ","pages":"24-7"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12558193","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}

引用次数: 0

Bispecific antibodies and targeted cellular cytotoxicity. Ostuni, Italy, June 13-17, 1992. 双特异性抗体和靶向细胞毒性。1992年6月13日至17日，意大利奥斯图尼。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

引用次数: 0

Possible targets on carcinoma for bMAb retargeting of lymphocyte or drug cytotoxicity. 肿瘤上bMAb淋巴细胞重靶向或药物细胞毒性的可能靶点。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

S Canevari, D Mezzanzanica, S Ménard, S Ferrini, L Moretta, M I Colnaghi

{"title":"Possible targets on carcinoma for bMAb retargeting of lymphocyte or drug cytotoxicity.","authors":"S Canevari, D Mezzanzanica, S Ménard, S Ferrini, L Moretta, M I Colnaghi","doi":"","DOIUrl":"","url":null,"abstract":"Retargeting of drugs or lymphocyte cytotoxicity through bi-specific monoclonal antibodies (bMAbs) has been proven a therapeutic tool against human carcinoma both in pre-clinical in vitro and in vivo studies. Some of these reagents have already been introduced into clinical trials and preliminary results appear to be promising. However, improvement of the specificity of this approach could be achieved by selecting more suitable target molecules on tumor cells. The research focused on developing MAbs directed against molecules with tumor-restricted distribution and homogeneous expression. Cell-membrane receptors for nutrients or growth factors which operationally represent tumor-specific molecules due to their overexpression, could be considered appropriate targets. Several bMAb anti-nutrients (the folate-binding protein) or growth-factor receptor (c-erbB1, c-erbB2)/anti-triggering molecules have been generated and all were able to efficiently retarget the relevant population of lymphocytes on tumor cells. In order to design a more reliable and selective therapeutic tool, the following parameters were analyzed: correlation between cytotoxicity and antigen level, potency and possible modulation of the target molecule.","PeriodicalId":77178,"journal":{"name":"International journal of cancer. Supplement = Journal international du cancer. Supplement","volume":"7 ","pages":"42-4"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12598985","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}

引用次数: 0

Novel surface molecules involved in human NK cell activation and triggering of the lytic machinery. 新表面分子参与人类NK细胞活化和触发的裂解机制。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

A Moretta, C Bottino, G Tripodi, M Vitale, D Pende, L Morelli, R Augugliaro, M Barbaresi, E Ciccone, R Millo

{"title":"Novel surface molecules involved in human NK cell activation and triggering of the lytic machinery.","authors":"A Moretta, C Bottino, G Tripodi, M Vitale, D Pende, L Morelli, R Augugliaro, M Barbaresi, E Ciccone, R Millo","doi":"","DOIUrl":"","url":null,"abstract":"Three new monoclonal antibodies (MAbs) termed 7A6, PP35 and A6/143 were isolated after mouse immunization with CD3- CD16+ NK clones. The screening procedure was based on the ability of MAbs to trigger cytolytic activity of the immunizing clones in a re-directed killing assay against the P815 murine mastocytoma cell line. The 7A6 MAb reacts with 58 kDa surface molecules that appear to belong to the same molecular family defined by the previously described NK-sub-set-specific GL183 and EB6 MAbs. However, unlike from these MAbs, the 7A6 MAb reacted with (and activated) all CD3- NK lymphocytes, independent of their sub-set assignment (based on the expression or lack of expression of EB6, GL183 and CD16). The PP35 MAb reacted with a 70 kDa surface molecule expressed on all CD3- NK cells, as well as on TCR gamma/delta + cells and on a small sub-set of TCR alpha/beta + CD8+ lymphocytes. The PP35 MAb induced activation of essentially all NK cells, although clonal analysis revealed quantitative differences in the magnitude of the cytolytic responses elicited in different clones. Finally, the A6/143 MAb reacted with a molecule of 115 kDa expressed by all human PBL. Similarly to 7A6 and PP35 MAbs, the A6/143 MAb activated all sub-sets of cloned NK cells.","PeriodicalId":77178,"journal":{"name":"International journal of cancer. Supplement = Journal international du cancer. Supplement","volume":"7 ","pages":"6-10"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12598990","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}

引用次数: 0

Bispecific IgG and IL-2 therapy of a syngeneic B-cell lymphoma in immunocompetent mice. 免疫功能正常小鼠同基因b细胞淋巴瘤的双特异性IgG和IL-2治疗。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

G J Weiner

{"title":"Bispecific IgG and IL-2 therapy of a syngeneic B-cell lymphoma in immunocompetent mice.","authors":"G J Weiner","doi":"","DOIUrl":"","url":null,"abstract":"Bispecific antibody (bsAb) which binds to CD3 and a tumor-associated antigen can induce lysis of tumor cells by T cells. Lymphocytes targeted by bsAbs are also capable of inhibiting the growth of human xenografts in athymic mice. However, little is known about the impact of this form of therapy in immunologically intact animals. The 38C13 murine B-cell lymphoma model is well suited for the study of bsAb therapy. BsAb, consisting of an IgG that is monospecific for both CD3 and the idiotype expressed by V 38C13 cells, was obtained from hybrid-hybridoma supernatant. Immunocompetent C3H mice were inoculated with V 38C13 cells and treated 2 days later with antibody. Over 90% of mice treated with monospecific antibody died of lymphoma, while only 27% of mice treated with bsAb developed tumor and died. In studies of bsAb/IL-2 synergy, treatment was delayed until 5 days after inoculation to allow for a larger tumor burden at the time of treatment. IL-2 was administered on days 3 to 6. All mice treated with IL-2 alone died of lymphoma, as did 75% of mice treated with bsAb alone. Only 18% of mice treated with both bsAb and IL-2 developed lymphoma. Thus, therapy with bsAb and IL-2 eliminated a tumor load 100- to 1000-fold greater than can be eliminated by therapy with anti-tumor antibody alone. These studies demonstrate the value of using immunocompetent animal models, and support the further exploration of bsAbs as an immunotherapy for human malignancy.","PeriodicalId":77178,"journal":{"name":"International journal of cancer. Supplement = Journal international du cancer. Supplement","volume":"7 ","pages":"63-6"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12598991","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}

引用次数: 0

CD28 co-stimulation of T-cell-mediated cytotoxicity. CD28共刺激t细胞介导的细胞毒性。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

M Azuma, J H Phillips, L L Lanier

引用次数: 0

Engineering a humanized bispecific F(ab')2 fragment for improved binding to T cells. 设计人源化的双特异性F(ab’)2片段以改善与T细胞的结合。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

M L Rodrigues, M R Shalaby, W Werther, L Presta, P Carter

{"title":"Engineering a humanized bispecific F(ab')2 fragment for improved binding to T cells.","authors":"M L Rodrigues, M R Shalaby, W Werther, L Presta, P Carter","doi":"","DOIUrl":"","url":null,"abstract":"We recently constructed a humanized bispecific antibody (BsF(ab')2v1) by separate E. coli expression of each Fab' arm followed by directed chemical coupling in vitro. BsF(ab')2 v1 (anti-CD3/anti-p185HER2) was demonstrated to retarget the cytotoxic activity of human CD3+ CTL in vitro against the human breast-tumor cell line, SK-BR-3, which over-expresses the p185HER2 product of the proto-oncogene HER2. Our minimalistic humanization strategy is to install as few murine residues as possible into a human antibody in order to recruit antigen-binding affinity and biological properties comparable to that of the murine parent antibody. This strategy proved very successful for the anti-p185HER2 arm of BsF(ab')2 v1. In contrast BsF(ab')2 v1 binds to T cells via its anti-CD3 arm much less efficiently than does the chimeric BsF(ab')2 which contains the variable domains of the murine parent anti-CD3 antibody. Here we have constructed additional BsF(ab')2 fragments containing variant anti-CD3 arms with selected amino acid replacements in an attempt to improve antibody binding to T cells. One such variant, BsF(ab')2 v9, was created by replacing 6 residues in the second hypervariable loop of the anti-CD3 heavy chain variable domain of BsF(ab')2 v1 with their counterparts from the murine parent anti-CD3 antibody. BsF(ab')2 v9 binds to T cells (Jurkat) much more efficiently than does BsF(ab')2 v1 and almost as efficiently as the chimeric BsF(ab')2. This improvement in the efficiency of T-cell binding of the humanized BsF(ab')2 is an important step in its development as a potential therapeutic agent for the treatment of p185HER2 over-expressing cancers.","PeriodicalId":77178,"journal":{"name":"International journal of cancer. Supplement = Journal international du cancer. Supplement","volume":"7 ","pages":"45-50"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12598986","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}

引用次数: 0

Targeting of T or NK lymphocytes against tumor cells by bispecific monoclonal antibodies: role of different triggering molecules. 双特异性单克隆抗体靶向T淋巴细胞或NK淋巴细胞对抗肿瘤细胞:不同触发分子的作用。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

S Ferrini, A Cambiaggi, C Cantoni, S Canevari, D Mezzanzanica, M I Colnaghi, L Moretta

{"title":"Targeting of T or NK lymphocytes against tumor cells by bispecific monoclonal antibodies: role of different triggering molecules.","authors":"S Ferrini, A Cambiaggi, C Cantoni, S Canevari, D Mezzanzanica, M I Colnaghi, L Moretta","doi":"","DOIUrl":"","url":null,"abstract":"MAbs directed against triggering surface molecules expressed by T lymphocytes (CD3, TCR, CD2, CD28) or by NK cells (CD2, CD16) are able to induce the functional program of these cells. These MAbs represent suitable reagents to construct biMAbs directed against TAA, in order to specifically target effector lymphocytes against tumor cells. Anti-CD3/anti-EGF-R biMAbs were constructed to specifically direct T lymphocytes against EGF-R+ tumor cells. Such biMAb are able to induce cytolysis of EGF-R+ tumor cell lines (A431, IGROV, KATO-III and U-87) by cytolytic CD3+ effector lymphocytes while tumor cells having low or absent expression of EGF-R were not lysed. In addition, both cytolytic T (CD8+) cells and non-cytolytic (CD4+) IL-2-expanded lymphocytes were able to secrete lymphokines upon contact with EGF-R+ tumor cells. To target NK cells against NK resistant ovarian carcinomas, we used an anti-CD16 Mab (IgG1) together with an anti-ovarian carcinoma MAb (IgG2a), to construct biMAbs using the hybrid hybridoma technique. The hybrid IgG1/IgG2a biMAb triggered the specific lysis of relevant target cells by resting NK cells and by a subset of NK clones. In addition, some TCR gamma/delta+ clones but not TCR alpha/beta+ clones could be targeted by the biMAb.","PeriodicalId":77178,"journal":{"name":"International journal of cancer. Supplement = Journal international du cancer. Supplement","volume":"7 ","pages":"15-8"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12599083","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}

引用次数: 0

Mechanisms of lymphocyte traffic and cell targeting. 淋巴细胞转运和细胞靶向机制。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

A Hamann

引用次数: 0

Initial experience in treating human lymphoma with a combination of bispecific antibody and saporin. 双特异性抗体与皂苷联合治疗人淋巴瘤的初步经验。

International journal of cancer. Supplement = Journal international du cancer. Supplement Pub Date : 1992-01-01

M A Bonardi, A Bell, R R French, G Gromo, T Hamblin, D Modena, A L Tutt, M J Glennie

{"title":"Initial experience in treating human lymphoma with a combination of bispecific antibody and saporin.","authors":"M A Bonardi, A Bell, R R French, G Gromo, T Hamblin, D Modena, A L Tutt, M J Glennie","doi":"","DOIUrl":"","url":null,"abstract":"Results are presented showing the use of bispecific F(ab')2 antibodies (bsAbs) in the delivery of saporin for the treatment of 2 human B-cell malignancies. BsAbs delivering saporin through CD22, but not through CD19, were effective at inhibiting the uptake of [3H]leucine by Daudi and Raji cells. Furthermore, a combination of 2 anti-CD22 bsAbs, selected to bind simultaneously to saporin, bound saporin 20 times more avidly and inhibited protein synthesis far more efficiently than any single bsAb. In the first patient, with end-stage chronic lymphocytic leukaemia (CLL), treatment with 10 mg of saporin complexed to 100 mg of anti-CD19 bsAb over 43 days showed no therapeutic effect. In contrast, the second patient, with end-stage non-Hodgkin's lymphoma (NHL), given 5 mg of saporin complexed with a pair (50 mg) of anti-CD22 bsAbs over 15 days showed a marked clinical response, including complete clearance of tumour from the blood, clearance of ascites and shrinkage of tumour masses. Neither patient experienced any toxic side-effects, either during or after treatment. However, the second patient developed a strong anti-mouse Fab (HAMA) response 28 days after the treatment started. No anti-saporin response could be detected.","PeriodicalId":77178,"journal":{"name":"International journal of cancer. Supplement = Journal international du cancer. Supplement","volume":"7 ","pages":"73-7"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12599568","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}

引用次数: 0