IMMUNOKINASES - Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges - page 324

FIGURE 21.5 Immunohistochemical analysis of selected organ sections after intravenously
injection of SCID mice with Hodgkin lymphoma-derived L540 cells, magnification x 4000. (a)
PBS control group shows tumor cell infiltration as analyzed by immunological detection of CD30 þ
cells. (b) DAPK2 0 -CD30L immunokinase group shows no evidence of tumor cell infiltration. Source:
Reproduced from Reference 6.

Immunohistochemical analysis with a mouse anti-human
CD30 monoclonal antibody revealed intensive staining
around the tumors, confirming the presence of the CD30
antigen (Figure 21.5). No tumor cells were detected in
mice treated with DAPK2 0 -CD30L.

REFERENCES

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21.5 OUTLOOK

Protein kinases are often deregulated in cancer, some being
more active and others less active than usual. DAPK2, a pro-
apoptotic serine/threonine kinase, falls into the latter cate-
gory, which means that it is a tumor suppressor protein and
that targeted restoration of its activity could help to induce
apoptosis in certain tumors. To avoid nonspecific effects on
normal cells, the immunokinase strategy was devised to
take advantage of both specific targeting and specific activ-
ity. By targeting CD30, a receptor that is predominantly
expressed on Hodgkin lymphoma-derived tumor cells, it
was possible to deliver DAPK2 directly into tumor cells
lacking kinase activity, resulting in selective restoration in
precisely those cells where the activity was required. We
were able to show that the purified recombinant immuno-
kinase fusion protein prevented tumor development in a
disseminated Hodgkin lymphoma model in SCIDmice, and
that treated animals remained disease free more than
100 days after single injection of DAPK2 0 -CD30L. Our
experiments provide an important proof of principle for
the immunokinase concept, and there is no reason why the
same strategy should not be applicable to other kinases that
are inactivated in tumor cells.