Compositions and methods for immunotherapy

Abstract

The present invention provides compositions and methods for immunotherapy, which include shelf-stable pharmaceutical compositions for inducing antigen-specific T cells. Such compositions are employed as components of an artificial antigen presenting cell (aAPC), to provide a patient with complexes for presentation of an antigen (e.g., a tumor antigen) and / or a T cell co-stimulatory molecule.

Description

PRIORITY[0001]This Application claims the benefit of, and priority to, U.S. Provisional Application No. 61 / 838,547, filed Jun. 24, 2013, and U.S. Provisional Application No. 61 / 948,916, filed Mar. 6, 2014, which are hereby incorporated by reference in their entireties.FIELD OF THE INVENTION[0002]The present invention relates to compositions, including pharmaceutical compositions, and methods that are useful for immunotherapy.BACKGROUND[0003]An antigen-presenting cell (APC) is a cell that processes and displays antigenic peptides in complexes with major histocompatibility complex (MHC) proteins on their surfaces. Effector cells, such as T-cells, may recognize these peptide-MHC (pMHC) complexes using receptors, such as T-cell receptors (TCRs).[0004]Dendritic cells (DCs) are an example of an antigen presenting cell that can be stimulated to effectively present antigen and support expansion of immune effect cells, thereby activating a cytotoxic response towards an antigen. In some immun...

AI Technical Summary

Benefits of technology

[0009]The co-stimulatory molecule may be conjugated to a solid support with antigen-presenting molecular complexes, to induce antigen-specific T cells. The antigen-presenting molecular complex may include MHC Class I and / or Class II complexes, or portions thereof comprising an antigen-binding cleft. In some embodiments, the molecular complex comprises one or more HLA amino acid sequences (e.g., comprises the extracellular domain of HLA or antigen-presenting portion thereof), which may contain additional sequences, such as immunoglobulin sequences, or other dimerizing or stabilizing sequence. HLA-Ig dimerizing fusions in some embodiments provide advantages in stability and / or binding affinity.

[0010]Thus, in some embodiments, the invention provides a bead- or particle-conjugated molecular complex for presentation of antigen to T cells, where the complex comprises an amino acid sequence forming a Class I or Class II antigen binding cleft, or portion thereof. The amino acid sequences of the antigen presenting complex may include fusions to heterologous sequences, to provide stability, affinity, and steric advantages, for example. In some embodiments, the heterologous sequences include immunoglobulin sequences. In some embodiments, the molecular complex includes HLA (e.g., HLA-A2) amino acid sequences fused to heterologous sequences, such as immunoglobulin sequences. In some embodiments, the immunoglobulin comprises a human heavy chain immunoglobulin sequence (e.g., IGVH4), which can include immunoglobulin constant sequences to provide dimeric HLA, and may optionally comprise variable region sequences. The variable sequences if present can be optionally modified to reduce or eliminate potential antigen binding, and optionally with no murine FW residues. The HLA amino acid sequence may be HLA-A*02:01 (IMGT Accession No. HLA00005) or a derivative thereof.

Problems solved by technology

However, DC immunotherapy, like many immunotherapies faces significant limitations.

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