One strategy for fighting aggressive cancer is adoptive T-cell therapy, which involves the transfer of effector T-cells (CTLs mainly, but also CD4+ T-cells) to restore T-cell responses in the host. Adoptive cell transfer therapy is the administration of ex vivo activated and expanded autologous (from the host) tumor-reactive T-cells, meaning that tumor specific T-cells are extracted from the patients, prepared and expanded into larger numbers in test tube, and then re-injected into the patients. However, for adoptive T-cell therapy to be effective in treating cancer, several events must occur:

1) T-cells must be activated in vivo through antigen-specific re-stimulation.

2) The T-cells must then expand to levels capable of causing the destruction of significant tumor burdens.

3) The anti-tumor cells must survive long enough to complete the eradiction of all tumor cells.

Current treatments do not fulfil all of the above mentioned critera and there is a need for a method of preparing a T-cell population for use in adoptive immunotherapy that increases proliferation and survival of antigen-specific T-cells during their activation.

The CD70-concept relates to an in vitro method for priming of antigen-specific T-cells (cytotoxic T lymphocytes, CTLs) suitable for administration to patients having a tumor. In summary, the invention is used to increase the survival of expanded tumor specific T-cells in adoptive immunotherapy.

As is mentioned above, the problem today is that expanded CTLs do not live long enough to elicit an effective antitumor response and research has been focused on prolonging the life of CTLs. This research has led to the knowledge that DCs that express CD70 are able to prolong the life on CD8+ T-cells (the kind of cells that become CTLs) when they encounter them. The problem today is however that it is very difficult to produce DCs which express CD70. Only two research groups, known to Immunicum, have managed in doing this, and their results are not encouraging. Immunicum however, has realized that alloreactive CD4+ T-cells, when mixed with DCs, will make DCs express CD70 in very high amounts. Immunicum’s concept thus both expands and prolongs the life of CD8+ T-cells (CTLs).

When the expanded tumor-specific CTLs are re-injected into the patient they are able to recognize and kill tumor cells, but what you want to achieve is another round of proliferation of CTLs to further expand them into even larger numbers. This can be achieved by simultaneously administering a vaccine, such as Immunicum’s core-concept or any other vaccine concept. Vaccination namely leads to an inflammation in the lymph nodes where tumor antigen-loaded DCs reside. Since CTLs are attracted to inflammatory milieus they will migrate to the draining lymph nodes where they encounter tumor antigen loaded DCs and are subsequently re-activated and expanded again into even larger numbers.

Immunicum’s concept can thus be used as a stand alone therapy, but will work even better if used in combination with another vaccine concept, thus making it attractive for most vaccine developers in the world that are looking for CTL responses. Both infections and cancers can be targeted.