| dc.contributor.author | Zhu, Zhenping. | en_US |
| dc.date.accessioned | 2014-10-21T12:33:41Z | |
| dc.date.available | 1993 | |
| dc.date.issued | 1993 | en_US |
| dc.identifier.other | AAINN93763 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55403 | |
| dc.description | Two monoclonal antibodies (MoAbs) directed against human B-cell chronic lymphocytic leukemia (CLL), i.e., Dal B01 (an IgG$\rm\sb{2a})$ and Dal B02 (an IgG$\sb1),$ reacted specifically with D$\sb{10-1}$ cells, a subclone of the Epstien-Barr virus (EBV) transformed human B-cell CLL line EBV-CLL-1. After intravenous (i.v.) injection into subcutaneous (s.c.) D$\sb{10-1}$ xenograft bearing nude mice, there was selective localization of radiolabeled Dal B01, Dal B02 or their F(ab)$\sp\prime\sb2$ fragments in the xenografted tumors. Excellent tumor images were obtained in mice given $\sp{131}$I-Dal B02, as well as in mice given $\sp{131}$I-Dal B02 F(ab)$\sp\prime\sb2$ fragment. Two chemotherapeutic agents, i.e., methotrexate (MTX) and adriamycin (ADR), were covalently linked to Dal B01 as well as Dal B02 using several different linkages. Both Dal B01-MTX and Dal B02-MTX conjugates demonstrated selective cytotoxicity towards target D$\sb{10-1}$ cells. In vitro uptake studies showed that D$\sb{10-1}$ cells took up much more Dal B01 or Dal B02 conjugated MTX than non-target MOLT-3 cells did, although MOLT-3 cells took up more MTX than D$\sb{10-1}$ cells did when incubated with free MTX. Four different types of Dal B01-ADR or Dal B02-ADR conjugates were prepared and their cytotoxicity was evaluated in vitro. One of these conjugates, i.e., Dal B02-Dex-ADR (ss), was found to be not only selectively cytotoxic to D$\sb{10-1}$ cells, but also was more potent than free ADR. Therapy in s.c. D$\sb{10-1}$ xenograft bearing nude mice with this conjugate demonstrated that at approximately equal toxic dose level, the antitumor activity of this conjugate was superior to that of free ADR, non-specific IgG$\sb1$-Dex-ADR (ss) conjugate, Dex-ADR binary conjugate or a mixture of Dex-ADR and Dal B02. | en_US |
| dc.description | To evaluate the antitumor activity of $\sp{131}$I labeled Dal B02, I developed two clinically relevant models of human B-cell CLL in SCID or irradiated nude mice by inoculating these mice i.p. or i.v. with D$\sb{10-1}$ cells. Hundred percent of tumor inoculated mice developed either ascites or solid tumors with metastases in lymph nodes and a number of internal organs and died within 5 to 7 weeks after tumor inoculation. Using these models, as well as a s.c. D$\sb{10-1}$ model described above, the antitumor activity of Dal B02, either alone or labeled with $\rm\sp{131}I,$ was investigated. Results revealed that, although Dal B02 itself had some antitumor effect, $\sp{131}$I labeled Dal B02 was the most potent tumor inhibitor. Treatment with 50 $\mu$g of Dal B02 linked to 300 $\mu$Ci of $\sp{131}$I resulted in significant tumor inhibition as well as complete cure in a proportion of mice in all the three models. | en_US |
| dc.description | Studies with an anti-human renal cell carcinoma (RCC) MoAb Dal K29-OKT3 heteroconjugate showed that after i.v. injection, this heteroconjugate selectively localized in xenografted s.c. Nu-caki-1 tumors in nude mice. In an ascites model of human RCC, treatment with this heteroconjugate along with human peripheral blood lymphocytes (PBLs) significantly prolonged the survival of tumor inoculated nude mice. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1993. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Immunology. | en_US |
| dc.title | Monoclonal antibody-based detection and treatment of human B-cell chronic lymphocytic leukemia/lymphoma and renal cell carcinoma in experimental models. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
