A synthetic strategy for conjugating small molecules and peptide-based therapeutics, via a cleavable ester bond, to a lipidated β 3 -tripeptide is presented. The drug-loaded β 3 -peptide was successfully co-assembled with a functionally inert lipidated β 3tripeptide to form a hydrogel. Quantitative release of lactose from the hydrogel, by the action of serum esterases, is demonstrated over 28 days. The esterase-mediated sustained release of the bioactive brain-derived neurotrophic factor (BDNF) peptide mimics from the hydrogel resulted in increased neuronal survival and normal neuronal function of peripheral neurons. These studies define a versatile strategy for the facile synthesis and co-assembly of self-assembling β 3 -peptide-based hydrogels with the ability to control drug release using endogenous esterases with potential in vivo applications for sustained localized drug delivery.
Adjuvant contact therapy with BCG can be used to control tumor deposits at local subcutaneous sites and at other sites, particularly pulmonary metastases and pleural tumor growths. This treatment method is generally quantitatively more effective than general immunostimulation, or active immunotherapy that employs vaccines of adjuvant and tumor cells. Furthermore, this treatment is effective in hosts that lack full immunocompetence, making it still feasible in immunosuppressed patients. The current evidence indicates that local activation of host macrophages is probably the essential effector mechanism of adjuvant contact therapy.
Summary.-Subcutaneous growth of immunogenic chemically induced rat sarcomata and a hepatoma was restricted when cells were injected into syngeneic animals in admixture with MER. Rats rejecting mixed inocula were immune to further challenge with the same tumour. Growth of a chemically induced mammary carcinoma which lacks detectable immunogenicity was suppressed when low cell inocula were injected in admixture with MER or intact BCG organisms, although animals were not immdne to re-challenge. These studies indicate that clinically MER may be a suitable alternative to BCG for contact suppression of tumour growth or incorporation into tumour cell: adjuvant vaccines for active immunotherapy.
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