Epitope synchronization in antigen presenting cells
OwnerJohn J. L. Simard, David C. Diamondinventors
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Abstract
Disclosed herein are vaccines and methods for inducing an immune response against cancer cells and cells infected with intracellular parasites. Vaccines having housekeeping epitopes are disclosed. The housekeeping epitope is formed by housekeeping proteasomes in peripheral cells, but not by professional antigen presenting cells. A vaccine containing a housekeeping epitope that is derived from an antigen associated with a peripheral target cell can thus direct an immune response against the target cell. Methods of treatment are also disclosed, which involve administering a vaccine having a housekeeping epitope.
Claims28
An isolated T cell expressing a T cell receptor specific for an MHC-peptide complex comprising a first housekeeping epitope, wherein the housekeeping epitope is derived from a first antigen associated with a first target cell.
An epitope cluster, the cluster being derived from an antigen associated with a target, the cluster comprising or encoding at least two sequences having a known or predicted affinity for an MHC receptor peptide binding cleft, wherein the cluster is a fragment of the antigen, wherein the cluster has the structure:
- X-P21-XaN-P2N-X(|bN|−1)-PΩ1-XaN-PΩN
- where:
- X is any amino acid naturally occurring in protein sequence;
- Xa and X(|b|−1) are strings of such amino acids of length ‘a’ and ‘|b|−1’, respectively,
- a indicates the number of amino acids between P21 and P2N, and (|b|−1) represents the number of amino acids between P2N and PΩ1;
- P21 is a first primary anchor and second residue of a first epitope;
- P2N is a first primary anchor and second residue of an Nth epitope;
- PΩ1 is a last primary anchor and C-terminal residue of the first epitope;
- and
- PΩN is a last primary anchor and C-terminal residue of the Nth epitope;
- 2≦N≦Nc, N indicating the Nth epitope of the cluster and Nc the total number of epitopes in the cluster;
- aN and bN defining the positional relationship between the 1st and Nth epitope.
Dependencies are inferred from the claim text.