Methods relating to activated dendritic cell compositions and immunotherapeutic treatments for subjects with advanced cancers

Abstract

The present disclosure provides partially mature and activated dendritic cells that produce levels of cytokines / chemokines, for example, one or any combination of, and / or all of IL-6, IL-8, IL-12 and / or TNF[alpha], that are correlated with improved clinical outcomes, significantly increased survival times and significantly increased times to tumor or cancer recurrence. The determined threshold amounts of these cytokines can be used for (i) a immunotherapeutic potency test for activated dendritic cells, (ii) selecting responder patients, (iii) rejecting non-responder patients, and (iv) to screen for dendritic cell activation or maturation agents that can also induce the production of the threshold amount of the cytokines / chemokines.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Patent Application Serial No. 62 / 219,058, filed September 15, 2015, which is hereby incorporated in its entirety for all purposes. Background technique [0003] Patients with unresectable, locally advanced or metastatic solid tumors have a poor prognosis with few treatment options, especially after failure of standard therapies. Amato, Semin. Oncol. 27: 177-186, 2000; Bramwell et al., Cochrane Database Syst. Rev. 3: Cd003293, 2003; Klelger et al., Ann. Oncol. 25: 1260-1270, 2014). There have been several promising recent advances in immuno-cancer therapy (Ito et al., Biomed. Res. Int. 2015:605478, 2015; West, JAMA Oncol. 1:115, 2015); however, in order to elicit an effective immune response against cancer , the immune system must first be sensitized to attack cancer cells. (Melero et al., Nat. Rev. Cancer 15:457-472, 2015). Specifically, tumor-specific antigens must b...

AI Technical Summary

Problems solved by technology

However, DCs constitute less than 1% of peripheral blood mononuclear cells, implying that there is not enough cellular material to generate the composition used to initiate and maintain tumor-specific immunity

Additionally, the use of such tumor antigens often results in monovalent immunogenic compositions or vaccines that lose efficacy if tumor cells downregulate expression of the antigen used in immunization

Furthermore, the requirement to produce tumor antigens under conditions required by Good Manufacturing Practice (GMP) adds additional costs to traditional DC-based immunization approaches

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