RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses

Schmitt, Michael; Schmitt, Anita; Rojewski, Markus; Chen, Jinfei; Giannopoulos, Krzysztof; Fei, Fei; Yu, Yaojun; Götz, Marlies; Heyduk, Marta; Ritter, Gerd; Speiser, Daniel E.; Gnjatic, Sacha; Guillaume, Philippe; Ringhoffer, Mark; Schlenk, Richard F.; Liebisch, Peter; Bunjes, Donald; Shiku, Hiroshi; Döhner, Hartmut; Greiner, Jochen

doi:10.1182/blood-2007-07-099366

Cited by 198 publications

(163 citation statements)

References 41 publications

(60 reference statements)

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“…These CTLs were able to induce the selective lysis of autologous RHAMM-expressing AML blasts, confirming the functionality of the vaccine-elicited immune response. 47 Similar results have been obtained with PR1, a nonameric HLA-A*0201-restricted peptide derived from proteinase 3 (amino acids (aa) 169-177). 73 The Molldrem group at the MD Anderson Cancer Center was the first to test the immunogenicity of PR1 peptide vaccination in a mixed cohort of patients with AML, CML and myelodysplastic syndromes.…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respsupporting

confidence: 67%

“…Majeti et al 29 compared the gene expression signature of LSCs with that of normal HSCs and identified over 3000 genes with dysregulated expression in LSCs. 29 The published data set also includes several genes encoding proteins that can be recognized by the immune system and act as LAAs, such as Elicited (T) 47,95 Natural (B/T) 25 …”

Section: Criterion 2: Frequency and Pattern Of Expressionmentioning

confidence: 99%

“…AurA, NuSAP1 and RHAMM are also required for mitotic spindle stability. 32,36,46,47 hTERT may confer a proliferative advantage to tumor cells by counteracting telomere shortening. Paradoxically, AML cells usually exhibit decreased expression of hTERT.…”

Section: Criterion 3: Oncogenicitymentioning

confidence: 99%

“…69 High in vivo immunogenicity has also been observed for RHAMM. In a phase I clinical trial of vaccination with the immunogenic RHAMM 165-173 epitope, Schmitt and coworkers 47 identified an increase in the frequency of circulating RHAMM-tetramer þ CD8 þ T cells in two out of three AML patients following vaccination. These CTLs were able to induce the selective lysis of autologous RHAMM-expressing AML blasts, confirming the functionality of the vaccine-elicited immune response.…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 99%

“…94 In a clinical trial of combined PR1/WT1 [126][127][128][129][130][131][132][133][134] peptide vaccination, Rezvani et al 73 demonstrated that the induction of high-avidity PR1-and/or WT1-specific CTLs was critically required to achieve clinical response (reduction of WT1 transcript levels). 73 Schmitt et al 47 assessed the clinical effectiveness of RHAMM 165-173 peptide vaccination in a mixed cohort of patients with hematological malignancies, including three patients with AML. 47 Immunization was followed by a marked decrease in bone marrow blast counts and a parallel increase in circulating RHAMM 165-173 -tetramer þ effector CD8 þ T cells in one of these patients, showing the potential clinical utility of RHAMM for targeted immunotherapy.…”

Section: Criterion 5: Clinical Relevancementioning

confidence: 99%

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Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

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The graft-versus-leukemia effect of allogeneic hematopoietic stem cell transplantation (HSCT) has shown that the immune system is capable of eradicating acute myeloid leukemia (AML). This knowledge, along with the identification of the target antigens against which antileukemia immune responses are directed, has provided a strong impetus for the development of antigen-targeted immunotherapy of AML. The success of any antigen-specific immunotherapeutic strategy depends critically on the choice of target antigen. Ideal molecules for immune targeting in AML are those that are: (1) leukemia-specific; (2) expressed in most leukemic blasts including leukemic stem cells; (3) important for the leukemic phenotype; (4) immunogenic; and (5) clinically effective. In this review, we provide a comprehensive overview on AML-related tumor antigens and assess their applicability for immunotherapy against the five criteria outlined above. In this way, we aim to facilitate the selection of appropriate target antigens, a task that has become increasingly challenging given the large number of antigens identified and the rapid pace at which new targets are being discovered. The information provided in this review is intended to guide the rational design of future antigen-specific immunotherapy trials, which will hopefully lead to new antileukemia therapies with more selectivity and higher efficacy.

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Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respsupporting

confidence: 67%