Targeted therapies make room, anti-CD79b agents are coming
Mené sur 85 patients atteints d'un lymphome diffus à grandes cellules B, cet essai de phase Ib/II évalue l'activité antitumorale préliminaire et la dose maximale tolérée du polatuzumab védotin dispensé en combinaison avec une immunochimiothérapie de type R-CHP ou G-CHP (durée médiane de suivi : 21,5 mois)
Several molecules are being investigated as targets of new anti-lymphoma therapies, such as bispecific antibodies, antibody–drug conjugates (ADC), and chimeric antigen–receptor T cells. B-cell receptor components represent important targets, and some anti-B-cell receptor agents have been established as standards of care in selected lymphomas. However, B-cell receptor molecules are unsuitable targets for antibody-based therapies because they are located inside cells; CD79 is an exception. CD79 (composed of subunits CD79a and CD79b) is a heterodimeric signal-transduction component of the B-cell receptor, ubiquitously expressed in mature B-cell lymphomas and placed on the cell surface by the earliest committed B-cell progenitors before expression of immunoglobulin
μ. Antibodies to CD79b induce negative cell signals and suppress response to T-cell-dependent antigens. However, unconjugated anti-CD79b antibodies induce modest B-cell depletion and show moderate antibody-dependent and complement-dependent cellular cytotoxicity, if any. Conversely, anti-CD79b antibodies might be suitable candidates for ADCs, which are tripartite molecules consisting of a cytotoxic agent conjugated to an anti-tumour antibody by a cleavable linker. Anti-CD79b ADCs are trafficked to a lysosomal-like compartment of B cells as part of antigen presentation,
and induce a prolonged and sustained depletion of proliferating B cells. Early clinical studies support these encouraging in-vitro observations, suggesting that anti-CD79b ADCs might be effective therapies against B-cell lymphomas.
The Lancet Oncology 2019