CD44 ligation with A3D8 antibody induces apoptosis in acute myeloid leukemia cells through binding to CD44s and clustering lipid rafts

Anti-CD44 mAb for the treatment of B-cell chronic lymphocytic leukemia and other hematological malignancies: evaluation of WO2013063498

“…Furthermore, it should be noted that anti-CD44 mAbs are a promising therapeutic opportunity in several others forms of cancer. Table 1 lists several preclinical studies reporting on the efficacy of this molecule [21,22,32,33,38,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. Moreover, clinical trials are being carried out in patients with metastatic and/or locally advanced CD44-expressing malignant solid tumors and in patients with acute myelogenous leukemia (this latter in combination with cytarabine) [65,66].…”

CD44 regulates the apoptotic response and promotes disease development in chronic lymphocytic leukemia

“…The mAbs IM7 and A3D8 have been described previously and elicit a proapoptotic response in other cancer models. 19,22,34,35,55 The anti-human CD44 mAb A3D8 causes apoptosis of acute myeloid leukemia cells. 18,19,22,56 In our experiments, both mAbs induced MCL1 reduction and caspase-mediated cell death in murine and human CLL.…”

“…19,22,34,35,55 The anti-human CD44 mAb A3D8 causes apoptosis of acute myeloid leukemia cells. 18,19,22,56 In our experiments, both mAbs induced MCL1 reduction and caspase-mediated cell death in murine and human CLL. Clearly, more extensive testing, addressing also the impact of soluble CD44, is needed before proceeding to clinical trials with any of these antibodies in CLL.…”

“…To exploit this by antibody-based targeting, we selected the anti-CD44 mAbs IM7 and A3D8 based on their capacity to inhibit tumor propagation in other hematologic malignancies. 19,22,29,30,34,35 Here, incubation with IM7 specifically reduced survival of cultured murine CLL B cells from Em-TCL1:CD44wt mice ( Figure 5A). As reported earlier, 34 the effect of IM7 was not mediated by complement-dependent cytotoxicity, since it demonstrated the same degree of apoptosis induction in serum-free conditions (not shown).…”

“…16 Certain inhibitory CD44 mAbs can induce apoptosis in myeloid leukemias via ligand blocking or by alternative functional activation. [17][18][19][20][21][22] Given the proposed participation of CD44 in prosurvival signaling in CLL, we wished to elucidate its functional contribution to leukemic development and its potential as a therapeutic target. Our results suggest that CD44 regulates antiapoptotic MCL1 expression via the ERK and AKT pathways.…”