Monoclonal antibodies: potential new therapeutic treatment against multiple myeloma

Abstract

Despite recent treatments, such as bortezomib, thalidomide, and lenalidomide, therapy of multiple myeloma (MM) is limited, and MM remains an incurable disease associated with high mortality. The outcome of patients treated with cytotoxic therapy has not been satisfactory. Therefore, new therapies are needed for relapsed MM. A new anticancer strategy is the use of monoclonal antibodies (MoAbs) that represent the best available combination of tumor cytotoxicity, environmental signal privation, and immune system redirection. Clinical results in patients with relapsed/refractory MM suggest that MoAbs are likely to operate synergistically with traditional therapies (dexamethasone), immune modulators (thalidomide, lenalidomide), and other novel therapies (bortezomib); in addition, MoAbs have shown the ability to overcome resistance to these therapies. It remains to be defined how MoAb therapy can most fruitfully be incorporated into the current therapeutic paradigms that have achieved significant survival earnings in patients with MM. This will require careful consideration of the optimal sequence of treatments and their clinical position as either short-term induction therapy, frontline therapy in patients ineligible for ASCT, or long-term maintenance treatment.

A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in Patients with Relapsed/Refractory Multiple Myeloma

“…Therapeutic monoclonal antibodies (mAbs) such as IPH2101 comprise just one dimension (28) of the promising, rapidly expanding field of immunotherapy for MM which also includes NK- and T-cellular therapies (29,30), vaccines (30) and immunomodulating agents, among others. Tumor-directed mAbs (31,32) as well as effector cell-targeted mAbs (21,22,33) provide an opportunity for increasing precision with which to modulate immunity against MM, as well.…”

Utility ofCD54,CD229, andCD319 for the identification of plasma cells in patients with clonal plasma cell diseases

“…At present, combined assessment of CD138 and CD38, together with CD45, FSC, and SSC, is considered the standard approach for the identification of normal and MM PCs. However, in recent years new therapeutic antibodies against a variety of PC surface molecules, including CD38 and CD138, have been developed and are currently under evaluation for the treatment of MM patients . Therapeutic usage of these classical PC markers hampers, at least to a certain extent, their utility for the detection of residual levels of PCs (i.e.…”

Activation of NK cells and disruption of PD-L1/PD-1 axis: two different ways for lenalidomide to block myeloma progression

“…In the last decade new approaches such as IPH-2102 (anti-KIR) mAb therapy and immune check-points inhibitors (ipilimumab (anti-CTLA-4) [48, 49, 94, 95] have made further progresses in solid tumors and hematological malignancies. However, their impact on MM cell functions and the NK/MM interaction has not been completely investigated.…”