Immune therapies for malignant mesothelioma

Abstract

Malignant mesothelioma (MM) is a rare disease which can develop in pleura, pericardium or peritoneum and in which the therapies available have limited efficacy and are associated with various side effects. Therefore, there is a need for more targeted and more effective therapies which are able to halt the disease progression. Among them immune therapies actively or passively directed against various structures of the MM cells seem to be particularly promising given their inhibitory potential demonstrated in both experimental and early clinical studies. Mesothelin in particular seem to be not only a biomarker of disease activity but also a therapeutic target. This review discusses the immune therapies currently investigated for MM.

Keywords::

• antibodies
• immunotoxin
• mesothelin
• mesothelioma
• vaccines

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Malignant mesothelioma (MM) is a rare disease with high unmet therapeutic need because the conventional therapy is not always able to induce a complete and sustained remission.

• Consequently, other therapies should be investigated in this disease, and immune therapies are of particular interest.

• Some of these therapies are represented by blocking antibodies that can target various molecules such as mesothelin, TGF-β, VEGF-A, EGFR or cytotoxic T lymphocyte-associated antigen 4.

• Antimesothelin immune therapies such as amatuximab are in the most advanced stage of clinical development exhibiting promising efficacy.

• Fusion proteins can also exert potent antitumor effect in MM, especially if combined with other antitumor therapies such as tyrosine kinase inhibitors or interleukins.

• Antitumor vaccines able to elicit immune responses against mesothelin or other tumor antigens are also investigated as potential therapies in MM, and the topic (intrapleural) route of administration for such compounds might be of particular interest in this setting.

• Most of such therapies are planned to be given in addition to the conventional therapies.

• However, in refractory MM, immune therapies might be given as monotherapies.

• Ideal immune therapies should be able to work in all histological subtypes of MM.