Combination of the Human Anti-CD30 Antibody 5F11 with Cytostatic Drugs Enhances Its Antitumor Activity against Hodgkin and Anaplastic Large Cell Lymphoma Cell Lines

Abstract

Due to its selective overexpression on the malignant cells of Hodgkin's lymphoma (HL) and large cell anaplastic lymphoma (ALCL), CD30 is an excellent target for immunotherapy of these diseases. The fully human monoclonal anti-CD30-antibody 5F11 has been shown to be effective against CD30-expressing cell lines both in vitro and in vivo. In addition, 5F11 shows promising antitumor activity in phase 1/2 clinical trials. To extend these promising results, the authors evaluated combinations of 5F11 with conventional cytostatic drugs against a variety of lymphoma cell lines in vitro. Most combinations tested showed at least additive cytotoxic effects on the HL-derived cell lines L428, L540, and L1236 and the ALCL-derived cell line Karpas 299 as measured by proliferation assays (XTT) and the induction of apoptosis (annexin-V FACS analysis). The most impressive results were detected with the combination of 5F11 and gemcitabine or etoposide. The data suggest that the combination of the human antibody 5F11 with conventional chemotherapy might be beneficial in the combined chemo-immunotherapy of CD30-positive lymphomas.

Sequential combination of gemcitabine, vinorelbine, pegylated liposomal doxorubicin and brentuximab as a bridge regimen to transplant in relapsed or refractory Hodgkin lymphoma

“…9,10,11 Moreover, the combination of cytostatic drugs such as gemcitabine with antiCD30mAB can really enhance the antitumor activity of the immunotherapy.…”

Multimodality Technologies in the Assessment of Hematolymphoid Neoplasms

“…16,17 Hematopathologists must be aware of such therapies because they can dictate the panel of immunohistochemical stains used and interpretation of those stains. For example, the use of rituximab to treat CD20 þ B-cell lymphomas may yield posttreatment B-cell proliferations that downregulate CD20 expression.…”

Immunotherapies for Hodgkin's lymphoma

“…In tumor cell lines and an HL xenograft model, giving bortezomib (a proteosome inhibitor that suppresses NK-kB activation) after 5F11 helped to overcome apoptotic resistance and had cytotoxic synergy [66]. In vitro data also suggest enhanced cytotoxicity when 5F11 is combined with chemotherapy including gemcitabine and etoposide [68]. Similarly, SGN-30 has been found Kasamon to sensitize tumor cells to a variety of cytotoxic agents; significant synergy with bleomycin, etoposide, and cytarabine was found in vitro, and potentially enhanced antitumor activity was noted with bleomycin in HL xenografts [67].…”