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Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures
- Viruses used for oncolytic therapy
- Oncolytic viruses
- T-VEC: name derivation
- T-VEC: engineered oncolytic HSV-1 strain
- Effects of ICP34.5 deletion
- T-VEC: local and systemic effects
- Potential action points of T-VEC
- Preclinical research of JS1/ICP34.5−/ICP47
- Preclinical research: GM-CSF expression
- Preclinical research: antitumour immune response
- Preclinical research: oncolysis in mT-VEC mice
- Preclinical research: CD8+ T cells & mT-VEC
- Melanoma in intralesional oncolytic immunotherapy
- Method of administration
- First in-human T-VEC study
- First in-human T-VEC study: biological activity
- T-VEC single-arm Phase 2 study design
- T-VEC single-arm Phase 2: effector T cells
- T-VEC single-arm Phase 2 study: response rates
- OPTiM phase III trial (005/05)
- Key eligibility criteria
- Disease characteristics: T-VEC arm in OPTiM
- Interval progression prior to T-VEC response
- Response of non-visceral lesions to T-VEC
- OPTiM endpoints
- Injected lesions response to T-VEC
- Non-injected non-visceral lesions & T-VEC
- Non-injected visceral lesions & T-VEC
- Secondary endpoint: overall survival (OS)
- Outcomes by key co-variates
- OS by stage and line of therapy
- Safety: adverse events (AEs)
- Pembrolizumab could enhance T-VEC action
- Preclinical research: combination therapy
- MASTERKEY-265 phase 1b study scheme
- Best change in tumor burden
- MASTERKEY-265 phase 3 study design
- Summary/Conclusions
Topics Covered
- Causing tumour cell lysis
- Initiating a specific systemic immune response
- T-VEC as an oncolytic HSV-1 strain
- Assessing cancer immunotherapy through melanoma
- Applicability of oncolytic viral therapy to various cancers
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Harrington, K. (2016, November 30). Talimogene laherparepvec: first-in-class oncolytic immunotherapy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 12, 2024, from https://doi.org/10.69645/JEVM8406.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Kevin Harrington has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Immunotherapy of Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
Hello,
my name is Kevin Harrington.
I work at the Institute
of Cancer Research in London.
I have a long-standing interest
in the development
of oncolytic viruses
as cancer therapies.
Today, I will be discussing
Talimogene Laherparepvec:
a First-in-Class
Oncolytic Immunotherapy.
0:18
Here are my disclosures.
0:27
For many years,
we have been interested
in the use of viruses
as potential therapies for cancer.
And on this slide, you can see
a small number of viruses
that have been
in active preclinical
and clinical evaluation
in the last two decades.
The rest of this talk
is going to focus on a single
example of this
which is the Herpes simplex virus,
which is now a registered therapy
with an approval
for the treatment of melanoma
in the USA, in Europe,
and in Australasia.
1:02
The principle of oncolytic viruses
rests on the fact
that certain viruses are capable
of infecting normal cells
where they will trigger
a potent antiviral response,
mainly based around
interferon signaling.
And this antiviral response
will shut down viral replication
and then as an additional
safety measure
will frequently trigger
the cell into apoptosis,
thereby protecting the host
against productive viral infection.
In certain situations,
these same viruses,
if they find themselves
infecting a cancer cell,
will be able to replicate.
And this is usually
based around the fact
that tumor cells frequently
lack normal
antiviral interferon
signaling responses.
As a consequence,
the productive replication of virus
is capable of mediating a process
of tumor lysis so called oncolysis,
leading to the release
of daughter virions,
which have the potential to cause
a cycle of ongoing replication
and infection in other tumor cells,
potentially leading
to a cancer specific infection.