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Clinical development of a dendritic-cell vaccine therapy for acute myeloid leukaemia

Periodic Reporting for period 3 - AML-VACCiN (Clinical development of a dendritic-cell vaccine therapy for acute myeloid leukaemia)

Reporting period: 2019-01-01 to 2020-09-30

AML-VACCiN is an international consortium that aims at developing a novel treatment strategy for the rare disease acute myeoloid leukaemia (AML). The main objective of AML-VACCiN is to test the potential of a novel vaccine treatment to prevent relapse in post-remission AML patients, by eradicating minimal residual disease (MRD). The objectives of the project are: 1) Determine the clinical response to vaccination with DCP-001, a multi-antigen dendritic cell vaccine (DCP-001) in postremission AML patients with MRD, via a Phase IIb study; 2) Identify and validate (immunological) biomarkers to predict a patient's response to vaccination with DCP-001; and 3) Gain further insights into the mode of action of DCP-001, and identify potential synergy of DCP-001 vaccination and other treatment modalities.
The work performed is in line with the initial objectives set out by the AML-VACCiN consortium.
1. To determine the clinical response to vaccination with an multi-antigen dendritic cell vaccine in post-remission MRD positive patients, the consortium has set up the ADVANCE II clinical study and opened up 10 clinical sites in the Netherlands, Germany, Norway, Sweden and Finland. AML patients have been treated at these sites with encouraging initial results in relation to control of MRD. These results have been recognized by the renowned 62nd ASH Annual Meeting and Exposition with an oral presentation by Van de Loosdrecht, MD, PhD and an abstract has been published. Fourteen patients have been enrolled at the moment of abstract submission of which four could be evaluated for MRD responses. Two patients became MRD negative at the first timepoint after initial vaccinations (week 14), and
remained negative until end of active follow-up (week 32), two other patients remained in CR, but with
MRD positivity.
2. Within the consortium a successful immumomonitoring program has been implemented, leading to
a highly standardized sample collection with excellent sample quality. Sample analysis included
profiling of the immune cells present in patient blood prior and post vaccination with a extensive
marker panel. In the immunomonitoring programm also IFNγ ELISPOT is included, a sensitive method
for quantification of the number of activated immune cells against known tumor associated proteins.
The first results showed that indeed vaccine-induced responses according to pre-defined response
criteria were observed against three well-known tumor associated antigens.
3. To get a more indepth understanding which mechanisms are triggered by DCP-001 vaccination and
how DCP-001 vaccination helps in the irradication of tumor cells, a pre-clinical model was set up by
consortium partner Bergen University, with as final goal to to investigate the suitability of DCP-001
vaccination in combination with standard AML drug therapies. Of particular interest were the agents
5-Azacitidine and Venetoclax that have recently emerged as a key therapy alternative for elderly and
unfit AML patients. These data firmly underscores the hypothesized mode of action of DCP-001 as a
cell-based vaccine which induces immune responses against leukemic cells.
The project results have large impact on the medical/scientific community given the encouraging
results seen in the ADVANCE II study that is set up by the AML-VACCiN consortium. With the aim to
control MRD and reduce relapse rates, this has a potentially large impact on patients suffering from
AML in the future.
Furthermore, the AML-VACCiN is also a close and broad collaboration between academic institutions
including academic hospitals and companies. Knowledge is readily shared between the consortium
members. Because of the nature of the DCP-001 product, being an ATMP, clinical development
challenges and involves all layers of the regulatory system, including national authorities and local
hospital ethical committees, as well as the development of manufacturing and logistics infrastructure.
The AML-VACCiN project greatly assisted in building a path for innovation from fundamental research
to patient care.
Lastly, the project is a true display of European collaboration with five countries participating and has
generated economic growth among its partners, with likely secondary effects. It also supports the
female participation rate which at consortium members is 86%.