Definitions:
Antigen Sensitized Dendritic Cells: are DCs which have been contacted with an antigen(s) for. which an increased immune response is desired. For example, an immature DC (see below) may be contacted with an antigen(s) for which an increased immune response is desired to form an antigen sensitized immature DC. The antigen can include a peptide, a protein, a carbohydrate, a lipid or combination. Cao (US Patent Application 16/959,103, published as US 2020/0338173)
Immature Dendritic Cells (DCs): have low T-cell activaiton potential. Immature DCs have not been stimulated with inflammatory cytokines such as for example, TNFalpha, IL6 or IL1alpha. Stimualtion with inflammatory cytokiens can switch DC to an immunostimualtory mode. This process is termed “maturation” and is associated with changes in DC phenotype and funciton, including up regulation of co-stimulatory and adhesion molecules and expression of distinct cheokine receptors. Cao (US Patent Application 16/959,103, published as US 2020/0338173)
Immature DCs may be identified based on typical morphology, expression of lower levels of MHCII and costimulatory molecuels adn the lack of expression of DC maturation markers such as CD83 and DC-LAMP and lack of CD14 expression. Exampels of positive markers for immature DCs also include DC-SIGN, intracellular CD83, Langerin and CD1A.
Mature Dendritic Cells (DCs_: are DCs that have been stimulated with inflammatory cytokines such as TNFalpha, IL6 or IL1 alpha. Cao (US Patent Application 16/959,103, published as US 2020/0338173)
Examples of markers for mature DCs include epxression of surface CD83, DC-LAMP, p55, CCR-7 and expression of high levels of MHCII and costimulatory molecules such as CD86. Cao (US Patent Application 16/959,103, published as US 2020/0338173)
Autologus DC Vaccines:
Conventional DC vaccines use DCs derived from autologous cells.
Exogenous DC Vaccines:
Exogenous DCs are DCs derived from any subject that is different from the patient. The DC may be cross-species, derived from a subject or the same or different species as the patient . Cao (US Patent Application 16/959,103, published as US 2020/0338173)
Antigen-sensitized Immature DCs:
Antigen-sensitized immature DCs have been used for immunotherapeutic purposes (WO 2013/107854). Kirkin (US 2013/0216584) also disclsoes vaccine compositions that include an antigen-sensitized immature DC that are immunocompetent stating that such immature DCs are able to induce strong antigne-specific CTL resposnes and that the DCs are loaded with tumor antigen to stimulate an anti-tumor specific CTL response.
Immature or semi-mature antigen-sensitized cells have also been adminstiered live and allowed to mature in vivo wehre they facilitate a toerogenic response (Xia, (2011) Rheumatology, 50:2187-2196; Dudek (2013) Front Immunol. vol 4, Article 438, pp. 1-14; Lutz (2002) Trends Immunol. 23(9): 445-449.
Cao discloses methods of formulating the vaccine which includes obtaining an immature DC, contacting the immature DC with an antigen to form an immature antigen sensitized DC and formulating the vaccine that includes the immature antigen sesnitized DC and a pharmaceutically acceptable carrier.
Cell fragments from Antigen-sensitized immature DCs:
Cell Fragments from antigen-sensitive DCs:
Palucka (WO 2008/005849A2) disclose that cell fragments of antigen-sensitized DCs may be used in compositions.
Cell Fragments from immature DCs:
Cao (US Patent Application 16/959,103, published as US 2020/0338173) discloses using cell fragments derived from immature DCs as vaccines. The patent discloses that it was surprisingly found the antigen senstitized immature desndritic cells elicit an earlier and better immunoresponse than mature DCs and that lysed antigen sensitized DCs work as well as live antigen sensitized DCs in inducing an immunoresponse. Such dead exogenous antigen sensitized immature DCs can significantly reduce the cost of storage, transport, preparation and transfer, and increase the availability, universality and effectiveness compared to conventional vaccines. In one embodiment, Cao discloses discloses formulating the vaccine which includes killing the DC as by sonication, heat treatment, lyophiliztion or combination, collecting the resulting cell debris and lyophilizing the cell debris into a powder and then in some embodiment sformulating the lyophilized cell debris or powder into a vaccine.