Survival benefit associated with human anti-mouse antibody (HAMA) in patients with B-cell malignancies

Azinovic, I.; DeNardo, Gerald L.; Lamborn, Kathleen R.; Mirick, Gary R.; Goldstein, D.; Bradt, Bonnie M.; DeNardo, Sally J.

doi:10.1007/s00262-006-0148-4

Cited by 38 publications

(27 citation statements)

References 30 publications

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“…21 In contrast, other groups have shown results that indicate that the development of HAMA may in fact prove to be beneficial in immunotherapy and this effect seems to be due to the capacity of some MAbs to induce the generation of cascades of antiidiotype antibodies that have survival advantage in tumor patients. [22][23][24] In our study, the antibodies generated in SCLC patients are directed predominantly against 1E10's idiotype and not against its isotype. The immunodominance of 1E10 MAb idiotype has been observed in all the animal species immunized with this MAb, 12 including cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

Neninger¹,

Díaz²,

Torre³

et al. 2007

Cancer Biology & Therapy

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ABSTRACT1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to an Ab1 MAb which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some human tumors. Preparations containing this Ab2 were capable to induce a strong anti-metastatic effect in tumor-bearing mice. We conducted a Phase I clinical trial to evaluate the toxicity and humoral immune response elicited by 1E10 vaccine in patients with small cell lung cancer (SCLC). Eligible patients were those who after received chemotherapy and/or radiotherapy had partial or complete response to treatment. Patients received four biweekly injections with 2 mg of aluminum hydroxide-precipitated 1E10 MAb, then other six doses at 28-day intervals, and later the patients who maintained a good performance status were reimmunized. Six patients with limited-stage disease and three with extensive-stage disease were enrolled in the study. Most of the patients who received at least four doses of 1E10 vaccine developed strong specific antibody responses against 1E10 MAb and NeuGc-GM3 ganglioside. Antibodies able to react with lung carcinoma tissue sections were detected in sera from vaccinated patients. A prolonged survival was observed in several patients treated with the anti-idiotype vaccine. No evidence of serious adverse effects was found.

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Section: Discussionmentioning

confidence: 99%

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

Neninger¹,

Díaz²,

Torre³

et al. 2007

Cancer Biology & Therapy

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“…The common responses include rashes, arthralgia, and myalgia (Maraveyas et al, 1994). It has been suggested that, in addition to any immediate effects of medication by the RIT, murine mAbs may result in a potential longer term benefit from a boost to the immune system provided by the HAMA response (Azinovic et al, 2006). If this hypothesis is correct, then the HAMA response as seen in the patients following pemtumomab treatment is encouraging.…”

Section: Pemtumomab (Theragyn)mentioning

confidence: 90%

核医学放射性核素治疗的研究现状及前景

Yeong

Cheng

2014

J. Zhejiang Univ. Sci. B

140

115

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Abstract:The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ( 131 I), phosphorous-32 ( 32 P), strontium-90 ( 90 Sr), and yttrium-90 ( 90 Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

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“…Preserved immune competence could be decisive in connection with the use of the unlabelled antibodies that develop efficacy based probably on ADCC and CDC as shown by different studies. Interestingly, a recent report, published while this article was reviewed (Azinovic et al, 2006), also described a survival benefit associated with HAMA.…”

Section: Toxicitymentioning

confidence: 92%

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

et al. 2006

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We present the long-term results of 18 chemotherapy relapsed indolent (N ¼ 12) or transformed (N ¼ 6) NHL patients of a phase II anti-CD20 131 I-tositumomab (Bexxar s ) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with 131 I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, 131 I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46 -70 months.

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Survival benefit associated with human anti-mouse antibody (HAMA) in patients with B-cell malignancies

Abstract: Patients with B-cell malignancies that developed high HAMA titers had longer survival that was not explained by risk factors or histologic grade, suggesting the importance of the immune system.

Cited by 38 publications

References 30 publications

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

核医学放射性核素治疗的研究现状及前景

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

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