Tumor regression activity

Results of chemical analysis showed that the glucosamine and total fatty acid contents of the KDO depleted, toxic lipid A and the nontoxic lipid A were essentially the same but that the nontoxic lipid A was significantly lower in the phosphorus content (Table V). The molar ratio of glucosamine phosphorus fatty acids was 2 2 4 for the toxic lipid A and 2 1 4 for the nontoxic lipid A. The relative molar distribution of normal fatty acids (lauric, myristic, and palmitic acids) and the 3-hydroxymyristic acid did not indicate a correlation between the content of these components and toxicity. The nontoxic lipid A possessed as high a tumor regression activity when combined with CWS as did the purified... 

We showed the existence of a toxic and a nontoxic lipid A fraction in the acid hydrolyzed endotoxin preparation (23). These two fractions were separated and the composition was determined on the purified components so that we could relate specific structural features of lipid A to both toxicity and tumor regression activity (23). 

Toxicity and Tumor Regression Activity of Purified Lipid A... 

Table XI. Toxicity and Tumor Regression Activity of Purified Lipid A Obtained from S. typhimurium G30/C21 ...

Conjugation of the 4-hydroxyandrostene nucleus as in 1,4,6 androstatriene-3,17-dione (ATD), conveys aromatase inhibitory and marked tumor regression activities (—80%) On the other hand, the introduction of a Cj-methyl into... 

Hamuro J, Hadding U, Bitter-Suermann (1978) Solid phase activation of alternative pathway of complement by p-l,3-glucans and its possible role for tumor regressing activity. Immunol 34 695-705... 

To review, in an experimental mouse model, LPDI/E7 vaccination both prevents the establishment of metastatic E7-expressing tumors in naive mice through an induced E7-specific T-cell immune response and, in mice with previously established E7-expressing tumors, causes tumor regression with one subcutaneous injection of LPDI/E7 [Han SJ, et al. Subcutaneous antigen loading of dendritic cells by liposome-protamine-DNA (LPD) nanoparticles results in their activation and induction of specific antitumor immune response (impublished)]. A robust immune response follows administration of LPDI/ peptide particles, which can be used as either a preventative or therapeutic cancer vaccination strategy due to the ability of the particles to prevent and eliminate tumors, respectively, in mouse models. 

A recombinant IFN-P, IFN-pia (Rebif Serono and Avonex Biogen) is produced for commercial use in Chinese hamster ovary (CHO) cells. A synthetic mutant produced in bacteria has a substitution of serine for cysteine at amino acid 17, yielding IFN-pib Betaseron Berlex). Both IFN-pia and IFN-pib are approved by the FDA for treatment of multiple sclerosis (MS) and have shown comparable biological activity (see Section 7.3). In vivo IFN-a2 and IFN-alb show comparable biological activity as well as similar side effects [54,55]. However, IFN-P is eliminated faster, resulting in no detectable serum peak levels [56]. The clinical consequence of this is not known. Objective responses, whether partial or complete tumor regression, have been documented in patients with carcinoma of the breast, hairy-cell leukemia, and non-small-cell lung cancer [57,58]. 

Three lipids A have been more intensively studied in animal models, all of them having indirect effects, mediated in vivo by the immune system. For two of them, DT-5461 and ONO-4007, TNF-a is an important mediator acting at the vascular level that provokes tumor necrosis. For the third one, OM-174, the treatment induces the accumulation of IFN-y and EL-1 P in tumors, which activate NOS II transcription in tumor cells that produce autotoxic NO, which then provokes the apoptosis of tumor cells. At the same time this treatment inhibits the production of TGF-pi by tumor cells which reduces the TGF-pi induced immunosuppression and enhances NO production. Acquired immune response, probably completes the tumor regression started by the apoptosis process and, most probably induces specific memory. 

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