Murine modelling of adoptive therapy for B cell lymphona

Abstract

The interaction between CD40 and its ligand (CD154) plays a critical role in the activation of the immune system.  Ligation of CD40 on antigen presenting cells (APC) enables them to process and present antigen efficiently and facilitates the generation of cytotoxic CD8+ T lymphocytes (CTL).  Such a response is observed using anti-CD40 mAb to generate CTL in the treatment of syngeneic murine lymphoma.  Adoptive transfer of CTL has proven effective in the clinic.  However, a major barrier for the use of adoptive transfer is in obtaining the large numbers of CTL needed for effective treatment.

Our aim was to study means of expanding lymphoma specific CTL ex vivo and to determine the optimal cell surface signalling and cytokine environment required.  In addition, we wished to investigate ways of prolonging the survival of these cells in the recipient mouse.

Here we show that CD62L^hi, CD44^low, CD25^low, CD49d^low, 41BB^low CD8+ T cells taken from the spleen of mice cured of the murine B cell lymphoma (BCL₁) via anti-CD40 treatment and not effector cells harvested from the peak of the CTL response nor naïve CD8+ T cells, can be used to generate CTL lines in vitro.  We also demonstrate that the activation, proliferation and cytotoxic activity of in vitro generated CTL is dependent on the presence of antigen.  We have shown that these CTL are specific for the tumour and are capable of long term expansion.  Furthermore, specific polyclonal lines of CTL have shown to be therapeutic in an adoptive transfer model.

Furthermore we show that, like CD8+ T cells, CD4+ T cells taken from the spleen mice cured of BCL₁ can be cultured in vitro to generate tumour-specific lines which augment the efficacy of CD8+ CTL lines in adoptive therapy.

More information

Identifiers

Catalogue record

Export record

ASCII CitationAtomBibTeXData Cite XMLDublin CoreDublin CoreEP3 XMLEndNoteHTML CitationHTML CitationHTML ListJSONMETSMODSMPEG-21 DIDLOpenURL ContextObjectOpenURL ContextObject in SpanRDF+N-TriplesRDF+N3RDF+XMLRIOXX2 XMLReferReference ManagerSimple Metadata