Cd30

Activated T lymphocytes, activated B lymphocytes, and activated NK cells58

Hodgkin's disease

"Anaplastic large cell lymphoma

"Agents currently in clinical trials, not yet FDA approved.

"Agents currently in clinical trials, not yet FDA approved.

surface proteins and therefore may act synergistically. Preliminary results show that combination therapy has been well-tolerated, with most patients demonstrating objective responses.58 It remains to be seen whether initial results will be confirmed upon further evaluation. However, combination therapy is an exciting therapeutic avenue to explore, potentially offering improved efficacy by targeting two different cell surface proteins.

Apolizumab(HUlDlO)

Apolizumab is another humanized IgGlMoAb currently under investigation. This compound is designed to target the antigenic determinant 1D10, which binds to the P chain variant of human leukocyte antigen-DR (HLA-DR). This 1D10 antigenic determinant is expressed primarily by lymphocytes, macrophages, and mesenchy-mal dendritic cells.62 While it is found on normal B lymphocytes, monocytes, and dendritic cells, it is also expressed on a proportion of NHL and CLL cells.63 A recent study evaluated flow cytometry immunopheno-typing of lymphoid malignancies in 105 patients <21 years of age. Results showed that 87/87 (100%) patients with pre-B cell ALL expressed HLA-DR and 3/3 (100%) patients with Burkitt lymphoma expressed this antigen. However, only 2 out of 11 (18%) patients with T-cell malignancies exhibited a positive result for HLA-DR.64 Thus, HU1D10 targets an important cell surface protein expressed in leukemias and lymphomas of B-cell origin. HU1D10 stimulates CMC, ADCC, and caspase-independent, direct apoptosis of cells expressing 1D10 antigen.62 63 A few phase I studies are currently evaluating patients with relapsed B-cell lymphomas; preliminary results indicate manageable toxicity, consisting mainly of grade 1-2 adverse effects.65-67 In one study, three of six patients with follicular lymphoma treated with 4 weekly infusions exhibited partial responses. These responses were delayed in nature, occurring at a median of 106 days and improving up to 400 days after treatment.66 Authors suggest a unique mechanism of action due to this pattern of response, and further studies may help clarify the activity of HU1D10, including a potential role in combination therapy.

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