| In vitro and in
vivo studies of the safety and efficacy of interleukin-2
delivery via PLGA microspheres with possible enhancement
through co-delivery of HTLV-I Tax protein Audrey S.Wang
Department of Biology,Massachusetts Institute of Technology,
Cambridge, MA 02139
Work conducted in the laboratory of
Prof. Robert Langer, Dept. of Chemical Engineering, MIT
|
| Non-Scientific
Abstract Interleukin-2 (IL-2), a potent
growth factor, is currently being used to combat cancer due to
its ability to enhance the responses of cytotoxic T cells
against tumor cells. To avoid the toxic side effects of high
IL-2 exposure, drug delivery involving the controlled and
sustained release of the protein from within polymer
microspheres was investigated. Safety and efficacy aspects were
addressed in cell culture and in rats. The HTLV-I Tax protein,
which has been shown to increase the number of IL-2 receptors
on T cells, was also evaluated as an accompanying component to
strengthen the IL-2 treatment.Cell culture studies showed a
positive effect of the Tax protein on cells grown with IL-2 but
no apparent effect in those grown without IL-2, possibly due to
insufficient stimulation of the cells in the latter condition.
In rats, the injected IL-2 microspheres did not greatly improve
their survival rate, but this delivery method did appear to
provide some protection from the toxic side effects seen in the
plainly injected IL-2.Overall, these initial results of IL-2
delivery via microspheres suggest that further studies may bear
great potential in developing a safer,more effective form of
anti-cancer treatment.
Abstract Interleukin-2 (IL-2), a
potent cytokine, is currently being used to combat cancer due
to its ability to enhance the responses of cytotoxic T
lymphocytes initiated by the immunological recognition of tumor
cells. To avoid the toxic side effects of systemic IL-2
exposure, drug delivery involving the controlled and sustained
release of the protein from within polymer microspheres was
investigated. Safety and efficacy aspects were addressed in
vitro and in vivo. The HTLV-I Tax protein,which has been shown
to induce the expression of the IL-2 receptor · subunit, was
also evaluated as a possible adjuvant to IL-2 immunotherapy.
Transfection studies showed that HuT-78 cells grown in the
presence of Tstim factor responded positively to transfection
of up to 2 µg HTLV-I tax DNA, but HuT-78 cells grown in the
absence of T-stim factor were relatively non-responsive,
possibly due to a lack of priming. In vivo, the
stereotactically injected IL-2 microspheres did not greatly
improve the survival rate of the Sprague-Dawley rats, but this
delivery method did provide some protection from the toxic side
effects seen in the plainly injected IL-2. Further studies need
to be performed in the HuT-78 cells to investigate the need for
priming cells prior to IL-2 delivery. |
