Methods for inducing CD8+ T cells to express a CD62L.sup.hiCD44.sup.lo naïve-like phenotype are provided. One embodiment provides a pharmaceutical composition containing CD8+ T cells induced to express a CD62L.sup.hiCD44.sup.lo naïve-like phenotype and optionally an excipient. The CD8+ T cells can be induced by contacting them with an effective amount of a MEK1/2 inhibitor. An exemplary MEK1/2 inhibitor is Selumetinib. The induced CD8+ cells can be used to treat cancer, reduce tumor burden, or treat infections in a subject in need thereof.

The present disclosure provides methods, uses, and kits for treating cancer in an individual. The methods comprise administering to the individual a PD-1 axis binding antagonist (such as an anti-PD-1 or anti-PD-L1 antibody) and an RNA vaccine (e.g., a personalized cancer vaccine that comprises one or more polynucleotides encoding one or more neoepitopes resulting from cancer-specific somatic mutations present in a tumor specimen obtained from the individual). Further provided herein are RNA molecules (e.g., a personalized RNA cancer vaccine that comprises one or more polynucleotides encoding one or more neoepitopes resulting from cancer-specific somatic mutations present in a tumor specimen obtained from the individual), as well as DNA molecules and methods useful for production or use of RNA vaccines.

Immune-based approaches to treat and prevent skin cancer by boosting T cell immunity against commensal HPVs present on skin. Thus, provided herein are compositions comprising: (i) a plurality of antigenic peptides each comprising a sequence of 9-30 amino acids derived from proteins from commensal human papilloma viruses, (ii) a plurality of live or live attenuated commensal human papilloma viruses, (iii) a plurality of antigenic proteins from commensal human papilloma viruses, preferably in virus-like particles, and/or (iv) a plurality of nucleic acids encoding (a) a plurality of antigenic peptides, each comprising a sequence of 9-30 amino acids derived from proteins from commensal human papilloma viruses or (b) a plurality of antigenic proteins from commensal human papilloma viruses; and optionally a T cell adjuvant that increases T cell response to the antigenic peptides.

Provided herein are recombinant antibodies and antigen-binding fragments thereof useful for binding to and inhibiting carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Also provided are methods of using the disclosed CEACAM1 antibodies and antigen-binding fragments thereof for reducing T-cell tolerance and for the treatment of cancer.

In one aspect, the present disclosure provides GlcNAc-Asn analogs of the formula (I): wherein the variables are as defined herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of using the compounds disclosed herein. Additionally, the present disclosure also provides methods of treating cancer comprising inhibiting NGLY1. ##STR00001##

Synthetic alphavirus-derived replicon expression systems comprising nucleic acid sequences encoding at least one modified nonstructural protein, and synthetic nucleic acid sequences encoding at least one heterologous protein are described. Methods of producing at least one heterologous protein in a cell, or of inducing an immune response in a subject by administering and/or expressing the synthetic alphavirus-derived replicon expression systems are provided.

A method for treating or reducing the incidence of recurrence of cancer, benign tumors, or HPV-associated lesions, including skin cancer, and particularly squamous cell carcinoma (SCC and basal-cell carcinoma, by administering one or more doses of HPV recombinant vaccine to a patient.

Described herein is an immunogenic composition comprising nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 19 to 50. Also described herein is an immunogenic composition comprising nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 141 to 272. Also described herein is an immunogenic composition comprising nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 273 to 322. Also described herein is an immunogenic composition comprising nucleic acid sequences encoding two or more amino acid sequences selected from the group consisting of SEQ ID NOs: 354 to 458.

siRNA sequences for inhibiting TGFβ and Cox-2 gene expression are provided. Methods for treatment of skin cancers, in which pharmaceutical compositions or containing these siRNA agents and complexes, are further provided, in particular, for treating squamous cell carcinoma (isSCC) and/or basal cell carcinoma (BCC). TGFβ and Cox-2 have each been implicated in driving cancer progression. TGFβ is upregulated in a number of tumor types and plays a role in stimulating cancer-associated fibroblast development. Cox-2 upregulation plays a negative role in inducing inflammation and converting active T-cells to inactive T-reg cells. Co-delivery of the two siRNAs into the same cell at the same time silences of both targets at the same time results in antitumoral activity.

A method for treating a microbial infection, especially pneumonia, comprising administering an aqueous-ethanol extract of Thymus or Boswellia or a composition containing the extract. Aqueous-ethanol extracts of Thymus and/or Boswellia.