Dataset Information

Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma.

ABSTRACT:

Background

Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies.

Methods

Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups.

Results

Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests.

Conclusion

We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients.

SUBMITTER: Roehnisch T

PROVIDER: S-EPMC4113220 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma.

Roehnisch Tim T Then Cornelia C Nagel Wolfgang W Blumenthal Christina C Braciak Todd T Donzeau Mariel M Böhm Thomas T Flaig Michael M Bourquin Carole C Oduncu Fuat S FS

Journal of translational medicine 20140509

<h4>Background</h4>Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies.<h4>Methods</h4>Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified parapro ...[more]

PMID: 24885819

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Project description:BackgroundImmune checkpoint blockade with monoclonal antibodies targeting programmed death 1 (PD-1) and its ligand PD-L1 has played a major role in the rise of cancer immune therapy. We have identified naturally occurring self-reactive T cells specific to PD-L1 in both healthy donors and cancer patients. Stimulation with a PD-L1 peptide (IO103), activates these cells to exhibit inflammatory and anti-regulatory functions that include cytotoxicity against PD-L1-expressing target cells. This prompted the initiation of the present first-in-human study of vaccination with IO103, registered at clinicaltrials.org (NCT03042793).MethodsTen patients with multiple myeloma who were up to 6 months after high dose chemotherapy with autologous stem cell support, were enrolled. Subcutaneous vaccinations with IO103 with the adjuvant Montanide ISA 51 was given up to fifteen times during 1 year. Safety was assessed by the common toxicity criteria for adverse events (CTCAE). Immunogenicity of the vaccine was evaluated using IFNγ enzyme linked immunospot and intracellular cytokine staining on blood and skin infiltrating lymphocytes from sites of delayed-type hypersensitivity. The clinical course was described.ResultsAll adverse reactions to the PD-L1 vaccine were below CTCAE grade 3, and most were grade 1-2 injection site reactions. The total rate of adverse events was as expected for the population. All patients exhibited peptide specific immune responses in peripheral blood mononuclear cells and in skin-infiltrating lymphocytes after a delayed-type hypersensitivity test. The clinical course was as expected for the population. Three of 10 patients had improvements of responses which coincided with the vaccinations.ConclusionVaccination against PD-L1 was associated with low toxicity and high immunogenicity. This study has prompted the initiation of later phase trials to assess the vaccines efficacy.Clinical trial registrationclinicaltrials.org, identifier NCT03042793.

Dataset Information

Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma.

Background

Methods

Results

Conclusion

Publications

Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma.

Similar Datasets

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