COMBINATION TREATMENT OF CD38-EXPRESSING TUMORS

1 - 108 . (canceled)

109 . A method for inhibiting growth and/or proliferation of tumor cells expressing CD38 in an individual in need thereof, which method comprises administration to the said individual of

i) a non-agonistic antibody which binds to CD38,

ii) at least one corticosteroid, and

iii) at least one non-corticosteroid chemotherapeutic agent selected from the group consisting of a proteasome inhibitor and a glutamic acid derivative.

110 . A method for treating cancer involving tumor cells expressing CD38 in an individual in need thereof, which method comprises administration to the said individual of:

i) a non-agonistic antibody which binds to CD38,

ii) optionally at least one corticosteroid, and

iii) optionally at least one non-corticosteroid chemotherapeutic agent, followed by autologous peripheral stem cell or bone marrow transplantation.

111 . The method of claim 109 , wherein said antibody is a full length IgG1 or IgM antibody.

112 . The method of claim 109 , wherein said antibody does not induce release of significant IL-6 by human monocytes or peripheral blood mononuclear cells.

113 . The method of claim 109 , wherein said antibody does not induce release of detectable IFN-γ by human T cells or peripheral blood mononuclear cells.

114 . The method of claim 109 , wherein said antibody is internalized by CD38-expressing cells.

115 . The method of claim 109 , wherein said antibody induces ADCC of CD38 expressing cells.

116 . The method of claim 115 , wherein said antibody induces ADCC with an EC50 value of below 15 ng/ml in multiple myeloma cells.

117 . The method of claim 109 , wherein said antibody induces CDC of CD38 expressing cells in the presence of complement.

118 . The method of claim 117 , wherein said antibody induces CDC with an EC50 value of below 5 μg/ml in Daudi-luc or CD38-CHO cells.

119 . The method of claim 109 , wherein said antibody inhibits the synthesis of cGDPR.

120 . The method of claim 119 , wherein said antibody inhibits the synthesis of cGDPR by at least 25 after 90 minutes at a concentration of 3 μg/ml.

121 . The method of claim 109 , wherein said antibody inhibits the synthesis of cADPR.

122 . The method of claim 121 , wherein said antibody inhibits the synthesis of cADPR by at least 25% after 90 minutes at a concentration of 3 μg/ml.

123 . The method of claim 109 , wherein said antibody competes with an antibody having a VL sequence of SEQ ID No:2 and a VH sequence of SEQ ID No:7; an antibody having a VL sequence of SEQ ID No:12 and a VH sequence of SEQ ID No:17 or an antibody having a VL sequence of SEQ ID No:22 and a VH sequence of SEQ ID No:27, for binding to CD38.

124 . The method of claim 109 , wherein said antibody is an antibody that specifically binds to a CD38 epitope that also is specifically bound by an antibody having a VL sequence of SEQ ID No:2 and a VH sequence of SEQ ID No:7; an antibody having a VL sequence of SEQ ID No:12 and a VH sequence of SEQ ID No:17; or an antibody having a VL sequence of SEQ ID No:22 and a VH sequence of SEQ ID No:27.

125 . The method of claim 124 , wherein said antibody binds to the regions SKRNIQFSCKNIYR and EKVQTLEAWVIHGG of human CD38 (SEQ ID NO:31).

126 . The method of claim 124 , wherein the binding of said antibody to human CD38 is sensitive to mutations at positions 272 and 274 of human CD38.

127 . The method of claim 124 , wherein said antibody is not able to bind to mutant CD38 wherein serine at position 274 is replaced by phenylalanine.

128 . The method of claim 109 , wherein said at least one corticosteroid comprises dexamethasone.

129 . The method of claim 109 , wherein said at least one corticosteroid comprises prednisone.

130 . The method of claim 109 , wherein said glutamic acid derivative is thalidomide or a thalidomide analog.

131 . The method of claim 130 , wherein said thalidomide analog is lenalidomide.

132 . The method of claim 128 , wherein said glutamic acid derivative is thalidomide or a thalidomide analog.

133 . The method of claim 132 , wherein said thalidomide analog is lenalidomide.

134 . The method of claim 109 , wherein said proteasome inhibitor is bortezomib.

135 . The method of claim 134 , wherein said at least one non-corticosteroid chemotherapeutic agent further comprises one or more agents selected from the group consisting of: melphalan, mechlorethamine, thioepa, chlorambucil, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, dacarbazine (DTIC), procarbazine, mitomycin C, cisplatin and other platinum derivatives, such as carboplatin.

136 . The method of claim 128 , wherein said proteasome inhibitor is bortezomib.

137 . The method of claim 136 , wherein said at least one corticosteroid comprises a glutamic acid derivative which is thalidomide or lenalidomide.

138 . The method of claim 109 , wherein said non-agonistic antibody, said at least one corticosteroid and said at least one non-corticosteroid chemotherapeutic agent are administered sequentially.

139 . The method of claim 109 , wherein said non-agonistic antibody, said at least one corticosteroid and said at least one non-corticosteroid chemotherapeutic agent are administered separately.

140 . The method claim 109 , wherein said antibody is administered in a dose of from 1 to 20 mg/kg.

141 . The method of claim 109 , wherein said antibody is administered once weekly for 2 to 12 weeks.

142 . The method of claim 109 , wherein said tumor cells expressing CD38 are from a B cell lymphoma, plasma cell malignancy, T/NK cell lymphoma or a myeloid malignancy.

143 . The method of claim 142 , wherein said tumor cells expressing CD38 are multiple myeloma cells.

144 . The method of claim 142 , wherein said tumor cells expressing CD38 are chronic lymhocytic leukemia cells.

145 . The method of claim 109 , wherein said tumor cells are recurrent or refractory tumor cells.

146 . The method of claim 109 , wherein said individual has not responded to a previous anti-cancer treatment for multiple myeloma.