It is known for some time that the immune cell composition of the lymphoma microenvironment is important because high numbers of tissue-infiltrating macrophages correlate with poor outcome in patients receiving chemotherapy but not in patients receiving the combination of chemotherapy and CD20-specific monoclonal antibody rituximab.
A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation.
We have set up a new in vivo model in nonimmunodeficient mice by stable transduction of the human CD20 cDNA in the murine lymphoma line EL4.Animals injected i.v. with the EL4-CD20(+) lymphoma cells died within 30 days with evident liver, spleen, and bone marrow involvement, confirmed by immunohistochemistry and PCR analysis.
Fusion proteins had reduced IFNalpha activity in vitro compared with native IFNalpha, but CD20 targeting permitted efficient antiproliferative and proapoptotic effects against an aggressive rituximab-insensitive human CD20(+) murine lymphoma (38C13-huCD20) and a human B-cell lymphoma (Daudi).
Our results, further supported by gene set enrichment analyses in a clinical data set of chronic lymphocytic leukemia patient samples exposed to a rituximab-containing treatment regimen, provide important mechanistic insights into the biologic complexity of anti-CD20-evoked tumor responses, and unveil cellular senescence as a hitherto unrecognized effector principle of the antibody component in lymphoma immunochemotherapy.
The study showed that lymphoma xenografts could be targeted in the presence of endogenous biotin when anti-CD20 fusion proteins containing SAv mutants (scFv(4)-SAv-S45A or scFv(4)-SAv-Y43A) were employed in combination with CA 2 and [(111)In]4b.
Treatment of patients with relapsed or refractory low grade follicular B-NHL lymphoma with rituximab (chimeric anti-CD20 mAb) has resulted in approximately 50% response rate.
Measles virus (MV)-PNP H(blind)antiCD20 is a CD20-targeted and prodrug convertase-armed MV that temporarily controls growth of lymphoma xenografts in severe combined immunodeficiency (SCID) mice in combination with fludarabine phosphate (fludarabine).
We have established a CD20- lymphoma cell line, RRBL1, from a diffuse large B-cell lymphoma with CD20- transformation from CD20+ follicular lymphoma after treatment with rituximab.
Both STINGa and TLRa induced cytokine release, modulated FcγR expression, and augmented mAb-mediated tumor cell phagocytosis <i>in vitro</i> However, only STINGa reversed the suppressive FcγR profile <i>in vivo</i>, providing strong adjuvant effects to anti-CD20 mAb in murine models of lymphoma.
This is the first identified case of loss of CD20 expression in a lymphoma that has relapsed after rituximab therapy, although several other cases have since been identified.
The cytotoxic effects of RDMs in combination with ultrasound (RDMs+US) were evaluated in vitro in CD20+ and CD20- cell lines, and its antitumor activities were assessed in Raji (CD20+) and Jurkat (CD20-) lymphoma cell-grafted mice.
The lymphoma cell was positive for CD20 and T cell lineage markers such as cytoplasmic CD3, CD4, and CD5 and had a monoclonal rearrangement of the T cell receptor (TCR) gamma chain gene.
The anti-CD20 monoclonal antibody rituximab has been less successful in treating chronic lymphocytic leukemia (CLL) than lymphoma, possibly due to the lower density of CD20 on B lymphocytes from CLL patients than on those from lymphoma patients.
We investigated combination therapy of IL-15 with rituximab in a syngeneic mouse model of lymphoma transfected with human CD20 and with alemtuzumab (Campath-1H) in a xenograft model of human adult T cell leukemia (ATL).