Radiotherapy is a frequently used strategy to fight cancer - however, this therapy
is seldom curative, and increasing evidence points to the great advantage of combining
radiation therapy with immunotherapy to increase the curative potential. Immunotherapy
has a great potential as cancer therapy, with the prospect of training our own immune
cells to actively kill cancer cells, not only targeting primary tumors, but also metastases.
Within this platform, one induces not only a treatment for current cancers, but could
potentially prevent recurrence in the future by the induction of an immune memory
response. In the current project (XVac, supported by the Danish innovation fund) we
are elucidating various strategies for combining radiation therapy and immune stimulatory
compounds. The primary goal of the XVac project is the development of new drug delivery
technology platforms, which can induce a potent anti-tumor immune response. We will
investigate how the combination of radiation and immunotherapy engages the immune
system. We will evaluate 1) the infiltration of immune cells to the tumor lesions,
2) systemic alterations in immune reactivity and immune regulation, and 3) the ability
to induce T-cell recognition of cancer specific antigens. These parameters will be
evaluated as markers of tumor rejection capacity in pre-clinical tumor models. Mutation-derived
antigens (neoantigens) are of prime interest as these provide a set of tumor specific
targets and are truly foreign to the immune system. For the identification of the
T-cell specific neoantigen landscaping pre- and post-immunization, a novel technology,
based on multimerized peptide-MHC-I coupled with a specific barcode, will be performed.
This technique gives the possibility of detecting >1000 antigen-specific T cells in
one sample. This will allow us to gain insight to T cells that recognize targeted
tumor cells and provide basis for rational design of personalized cancer vaccines.
Radiotherapy is effective, but does not effectively stimulate a specific immunogenic
eradication of all cancer cells. With the combination of immunotherapy this could
be overcome. The end goal of this project is to find effective and safe delivery mechanisms
of immune stimulatory compounds that can provide sustained clinical efficacy in cancer
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P08. Monitoring of immunotherapy P08.01
© 2018 Published by Elsevier Inc.