Many of the efforts toward developing vaccines against human malignancies have been frustrated by the lack of identification of a tumor-specific antigen that would allow tumor cells to be distinguished from normal cells. Idiotypic determinants of the surface immunoglobulin (Ig) associated with a given patient's B-cell lymphoma are unique to that tumor, and can thus serve as a tumor-specific marker. When conjugated to the immune carrier keyhole limpet hemocyanin (KLH), vaccination with an idiotype protein vaccine has been able to improve length of freedom from disease relapse in patients with follicular lymphoma (FL) in a minimal residual disease (MRD) state after induction therapy, as demonstrated in a recent randomized, controlled phase III trial. In addition to predictive biomarker discovery, using residual autologous tumor and blood samples from patients vaccinated on the phase III trial, we have now developed a next generation idiotype DNA vaccine with the goal of reducing vaccine production time while maintaining efficacy. A first-in-human study is planned to evaluate its use in patients with asymptomatic phase lymphoplasmacytic lymphoma.

01 Mar 2012·BloodQ1 · MEDICINE

Conjugation of lymphoma idiotype to CD40 antibody enhances lymphoma vaccine immunogenicity and antitumor effects in mice

Q1 · MEDICINE

Article

Author: Dickinson, Robert ; Carlring, Jennifer ; Heath, Andrew W. ; De Leenheer, Evy ; Szabo, Marika J.

AbstractPersonalized immunotherapy of lymphoma based on tumor idiotype (Id) has shown anti-idiotype humoral immune responses in 40%-50% and cellular immune responses in 50%-75% of follicular lymphoma patients, indicating that this therapy can be clinically successful. We have developed a novel vaccine against lymphoma consisting of an anti-CD40 Ab (ADX40) chemically conjugated to the tumor idiotype A20 and tested it in a murine lymphoma model. BALB/c mice were immunized with 2 doses of immunogen alone or in conjunction with additional adjuvants before tumor challenge. ADX40-Id vaccination resulted in significantly retarded tumor growth and reduced mouse morbidity. Moreover, similar mouse survival was obtained with 2 injections of ADX40-Id as with 8 injections using the standard therapy of keyhole limpet hemocyanin Id + GM-CSF. Co-administration of ADX40-Id with 3-O-deacyl-4′-monophosphoryl lipid A further significantly enhanced vaccine efficacy, resulting in an increased overall survival. Anti-Id–specific Abs were detected at elevated levels after ADX40-Id immunization; however, in vivo depletion of CD4 and/or CD8 T cells before challenge showed that CD8 effector T cells were the major mediators of tumor protection. The results of the present study show that the ADX40-Id conjugate vaccine is a potential candidate as a stand-alone vaccine or in combination with currently licensed adjuvants for lymphoma immunotherapy.

100 Deals associated with Lymphoma DNA vaccine(Genvax)

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphoma	Phase 2	United Kingdom	Genvax Technologies, Inc	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2004	Not Applicable	Follicular Lymphoma	155	idiotypic vaccination (Humoral anti-Id IR)	(uazobtczsw): relative benefit = 2.45 (95% CI, 1.5 - 4.0), P-Value = 0.0004	-	15 Jul 2004
				idiotypic vaccination (Cellular anti-Id IR)

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