VAC2 is an allogeneic, or non-patient specific, cancer vaccine candidate designed to stimulate patient immune responses to telomerase which is commonly expressed in cancerous cells but not in normal adult cells. VAC2, which is produced from our pluripotent cell technology using a directed differentiation method, is comprised of a population of mature dendritic cells. As the most potent type of antigen presenting cell in the body, dendritic cells instruct our body’s immune system to attack and eliminate harmful pathogens and unwanted cells. To target cancerous cells, VAC2 is engineered to express the tumor-selective antigen telomerase, which is found in over 85% of all cancers. Because the tumor antigen is loaded exogenously into the dendritic cells prior to administration, VAC2 is a platform technology that can be modified to carry any antigen, including patient-specific tumor neo-antigens.
Cancer, which afflicts millions worldwide, is one the largest unmet clinical needs with current treatment options providing limited efficacy and a wide range of debilitating side effects. The use of pluripotent cells as the starting material for VAC2 production adds several additional advantages to this candidate therapeutic. In comparison to technologies that rely on the use of a patient’s own blood, our pluripotent cell technology provides a scalable system for production of a large number of vaccine doses in a single lot, lower manufacturing costs, greater product consistency, and off-the-shelf availability to provide broader access to patients. In addition, we believe that as an allogeneic therapy, VAC2 has the potential to stimulate a more robust immune response through an adjuvant effect resulting from the partial immune mismatch between the VAC2 cells and patients receiving the therapy.
Potential Advantages of the VAC2 Approach
- Single master cell bank for scalability and consistency
- Available ‘off-the-shelf’, on demand
- No known significant off-target effects
- Low AE-related cost of treatment
- Lower anticipated COGS than CAR-T
- In combination with chemotherapy
- In combination with immune checkpoint inhibitors
VAC2 was designed to overcome limitations of first-generation I-O combinations and autologous approaches, while providing cost and safety advantages in combination or competition with CAR-T, CTL4, or ICIs.
Clinical development of VAC2 is being conducted through a partnership with Cancer Research UK (CRUK), who is responsible for costs and to conduct manufacturing and the clinical trial. Currently, enrollment is ongoing in a Phase 1 study of VAC2 in advanced and resected non-small cell lung cancer (NSCLS). The primary endpoint of this study is safety and tolerability of 6 intradermal injections. In May 2020, Lineage announced the early exercise of its option with Cancer Research UK for this immune-oncology cell therapy program as well as a platform expansion to include coronavirus vaccine development.
In October 2020, Lineage announced encouraging preliminary results from the ongoing Phase 1 clinical study of VAC2 in NSCLC. VAC2 demonstrated remarkably potent induction of immune responses in all patients dosed to date, with high levels of peripheral antigen-specific immunogenicity observed at multiple time points and confirmed by multimer staining. VAC2 also appears to be well tolerated with no unexpected adverse events reported. On the basis of these findings, and following completion of the ongoing VAC2 clinical study in NSCLC, the Company will seek to evaluate VAC2 in combination with therapies considered biologically complementary to VAC2, such as chemotherapy and the immune cell protectant properties offered by anti-PD1 immunotherapy.
In April 2021, Lineage announced a worldwide license and development collaboration agreement with Immunomic Therapeutics, Inc. to generate a novel product candidate derived from Lineage’s VAC allogeneic cancer immunotherapy platform and targeting a proprietary Tumor Associated Antigen (TAA) construct provided by Immunomic for the treatment of glioblastoma multiforme (GBM).
The VAC platform has broad application. We plan to investigate several approaches, including:
- In combination with immune checkpoint inhibitors (ICIs), with or without chemotherapy, to stimulate endogenous T cell response to enable ICIs to work better in “immune cold” tumors.
- ICIs make tumors more susceptible to immune function, potentially boosting the impact of DC immunotherapy by reducing cancer cell resistance.
- Ex vivo functional studies with glioblastoma tissue have shown that PD-1 blockade in combination with DC therapy results in increased survival compared to PD-1 or DC alone (Antonios et al. JCI Insight 2016).
- Proof-of-concept for a DC-ICI combination has been demonstrated in humans with multiple myeloma (Rosenblatt et al. ASH 2015).
- As new, targeted, and/or additional antigens given that allogeneic and autologous platforms can be used to deliver any antigen(s), including neoantigens; and
- As monotherapy in minimal residual disease with high risk of relapse aiming to stimulate T cell response to eliminate residual cancer cells after debulking methods such as chemotherapy, surgery, and radiotherapy.
Dendritic cell vaccine added to PD-1 blockade rescues the survival benefit in mice with established tumor burden
View our pipeline to see our other programs in development.