Improved outcome when B-cell lymphoma is treated with combinations of immunoliposomal anticancer drugs targeted to both the CD19 and CD20 epitopes.
OBJECTIVE
We have reported previously that successful immunoliposomal drug therapy with liposomal doxorubicin (DXR) against xenograft B-lymphoma models required targeting against an internalizing B-cell antigen, CD19 (P. Sapra and T. M. Allen. Cancer Res 2002;62:7190-4.). Here we compare targeting of immunoliposomal formulations of DXR with vincristine (VCR) targeted against CD19 versus a noninternalizing (CD20) epitope. We also examine the effect of targeting immunoliposomes with antibody combinations in an attempt to increase the total number of binding sites (apparent antigen density) at the target cell surface.


METHODS
Cell association of immunoliposomes (CD19-targeted, CD20-targeted, or combinations of the two) with human B-cell lymphoma (Namalwa) cells were studied using radiolabeled liposomes. Therapeutic efficacy of the same formulations was determined in a severe combined immunodeficient murine model.


RESULTS
Therapeutic results in severe combined immunodeficient mice bearing Namalwa cells administered anti-CD20-targeted liposomal DXR were barely improved over those found for nontargeted liposomal DXR or free DXR but, surprisingly, administration of anti-CD20-targeted liposomal VCR resulted in a significantly improved therapeutic outcome compared with nontargeted liposomal VCR, free VCR, or anti-CD20-targeted liposomal DXR. Treatment of murine B lymphoma with single injections of combinations of anti-CD19- and anti-CD20-targeted liposomal VCR led to cures in 70% of mice. However, mice injected with similar combinations of liposomal DXR did not have improved survival rates over anti-CD19-targeted liposomal DXR by itself.


CONCLUSIONS
The success of immunoliposomal therapy in combination regimens varies with the type of encapsulated drug and the nature of the target epitopes.
Sapra
Puja
P
Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Allen
Theresa M
TM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000737:chemistry; D018941:Antigens, CD19 / Q000737:chemistry*; D018951:Antigens, CD20 / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use; D004337:Drug Carriers; D000939:Epitopes; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D008024:Ligands; D008081:Liposomes / Q000737:chemistry*; D016393:Lymphoma, B-Cell / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D004337:Drug Carriers; D000939:Epitopes; D008024:Ligands; D008081:Liposomes; D014750:Vincristine; D004317:Doxorubicin