US 2023/0346906 A1 · CANCER TREATMENT STRATEGIES USING ARENAVIRUS VECTORS

Abstract

The present application relates generally to cancer treatment strategies using arenavirus particles. The treatment strategies described herein are for treating cancer, including head and neck squamous cell carcinoma, using tri-segmented arenavirus particles encoding a human papillomavirus (HPV) antigen. The treatment strategies described herein can include administration of an immune checkpoint inhibitor.

Claims119

Dependent claims

A method for treating cancer in a patient in need thereof comprising administering to the patient an effective amount of engineered replication-competent tri-segmented arenavirus particles comprising two S-segments encoding a fusion protein of human papillomavirus strain 16 (HPV16) E7/E6, wherein the effective amount is about 5×105 replication-competent virus focus-forming units (RCV FFU).

A method for treating cancer in a patient in need thereof comprising administering to the patient an effective amount of engineered replication-competent tri-segmented arenavirus particles comprising two S-segments encoding a fusion protein of human papillomavirus strain 16 (HPV16) E7/E6, wherein the effective amount is about 5×106 replication-competent virus focus-forming units (RCV FFU).

A method for treating cancer in a patient in need thereof comprising administering to the patient an effective amount of engineered replication-competent tri-segmented arenavirus particles comprising two S-segments encoding a fusion protein of human papillomavirus strain 16 (HPV16) E7/E6, wherein the effective amount is about 5×107 replication-competent virus focus-forming units (RCV FFU).

A method for treating cancer in a patient in need thereof comprising administering to the patient an effective amount of engineered replication-competent tri-segmented arenavirus particles comprising two S-segments encoding a fusion protein of human papillomavirus strain 16 (HPV16) E7/E6, wherein the effective amount is about 5×108 replication-competent virus focus-forming units (RCV FFU).

A method for treating cancer in a patient in need thereof comprising administering to the patient an effective amount of engineered replication-competent tri-segmented arenavirus particles comprising two S-segments encoding a fusion protein of human papillomavirus strain 16 (HPV16) E7/E6, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU).

A method for treating cancer in a patient in need thereof comprising one or more session, wherein each session comprises

i. administering to the patient an effective amount of engineered replication-competent tri-segmented arenavirus particles comprising two S-segments encoding a fusion protein of human papillomavirus strain 16 (HPV16) E7/E6 derived from a first arenavirus species, wherein the effective amount is about 5×105, 1×106, 5×106, 1×107, 5×107, 1×108, 5×108, or 1×109 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of engineered replication-competent tri-segmented arenavirus particles comprising two S-segments encoding a fusion protein of HPV16 E7/E6 derived from a second arenavirus species at a time point around half of the session, wherein the effective amount is about 5×105, 1×106, 5×106, 1×107, 5×107, 1×108, 5×108, or 1×109 RCV FFU.

A method for treating cancer in a patient in need thereof comprising administering to the patient an effective amount of Construct 1, wherein the effective amount is about 5×105, 5×106, 5×107, 1×108, or 5×108 replication-competent virus focus-forming units (RCV FFU), and wherein Construct 1 is administered intravenously with a frequency of every 3 weeks for 4 cycles followed by ongoing cycles with a frequency of every 6 weeks.

A method for treating cancer in a patient in need thereof comprising

(i) administering to the patient an effective amount of Construct 1, wherein the effective amount is about 5×105, 5×106, 5×107, 1×108, or 5×108 replication-competent virus focus-forming units (RCV FFU), and wherein Construct 1 is administered intravenously with a frequency of every 3 weeks for 4 cycles followed by ongoing cycles with a frequency of every 6 weeks;
and
(ii) administering to the patient 200 mg of pembrolizumab intravenously with a frequency of every 3 weeks or 400 mg of pembrolizumab intravenously with a frequency of every 6 weeks.

A method for treating cancer in a patient in need thereof comprising multiple sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×106 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×106 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

1 more element

A method for treating cancer in a patient in need thereof comprising multiple sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×107 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×106 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

1 more element

A method for treating cancer in a patient in need thereof comprising multiple sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×107 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×107 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

1 more element

A method for treating cancer in a patient in need thereof comprising multiple sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×107 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

1 more element

A method for treating cancer in a patient in need thereof comprising multiple sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 1×108 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

1 more element

A method for treating cancer in a patient in need thereof comprising multiple sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×108 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

1 more element

A method for treating cancer in a patient in need thereof comprising

(1) multiple sessions of administering Construct 2 and Construct 1, wherein each session comprises
i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×106 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×106 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks;
and
(2) administering to the patient 200 mg of pembrolizumab intravenously at a frequency of every 3 weeks or 400 mg of pembrolizumab intravenously at a frequency of every 6 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) multiple sessions of administering Construct 2 and Construct 1, wherein each session comprises
i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×107 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×106 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks;
and
(2) administering to the patient 200 mg of pembrolizumab intravenously at a frequency of every 3 weeks or 400 mg of pembrolizumab intravenously at a frequency of every 6 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) multiple sessions of administering Construct 2 and Construct 1, wherein each session comprises
i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×107 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×107 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks;
and
(2) administering to the patient 200 mg of pembrolizumab intravenously at a frequency of every 3 weeks or 400 mg of pembrolizumab intravenously at a frequency of every 6 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) multiple sessions of administering Construct 2 and Construct 1, wherein each session comprises
i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×107 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks;
and
(2) administering to the patient 200 mg of pembrolizumab intravenously at a frequency of every 3 weeks or 400 mg of pembrolizumab intravenously at a frequency of every 6 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) multiple sessions of administering Construct 2 and Construct 1, wherein each session comprises
i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 1×108 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks;
and
(2) administering to the patient 200 mg of pembrolizumab intravenously at a frequency of every 3 weeks or 400 mg of pembrolizumab intravenously at a frequency of every 6 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) multiple sessions of administering Construct 2 and Construct 1, wherein each session comprises
i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×108 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks;
and
(2) administering to the patient 200 mg of pembrolizumab intravenously at a frequency of every 3 weeks or 400 mg of pembrolizumab intravenously at a frequency of every 6 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) administering intratumorally to the patient an effective amount of Construct 1, wherein the effective amount of Construct 1 is about 5×106 replication-competent virus focus-forming units (RCV FFU);
and
(2) 3 weeks later administering to the patient multiple sessions, wherein each session comprises
i. administering intravenously to the patient an effective amount of Construct 2, wherein the effective amount is about 1×106 RCV FFU;
and
ii. administering intravenously to the patient an effective amount of Construct 1 at a time point around half of the session, wherein the effective amount is about 5×106 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) administering intratumorally to the patient an effective amount of Construct 1, wherein the effective amount of Construct 1 is about 5×106 replication-competent virus focus-forming units (RCV FFU);
and
(2) 3 weeks later administering to the patient multiple sessions, wherein each session comprises
i. administering intravenously to the patient an effective amount of Construct 2, wherein the effective amount is about 1×107 RCV FFU;
and
ii. administering intravenously to the patient an effective amount of Construct 1 at a time point around half of the session, wherein the effective amount is about 5×106 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) administering intratumorally to the patient an effective amount of Construct 1, wherein the effective amount of Construct 1 is about 5×107 replication-competent virus focus-forming units (RCV FFU);
and
(2) 3 weeks later administering to the patient multiple sessions, wherein each session comprises
i. administering intravenously to the patient an effective amount of Construct 2, wherein the effective amount is about 1×107 RCV FFU;
and
ii. administering intravenously to the patient an effective amount of Construct 1 at a time point around half of the session, wherein the effective amount is about 5×107 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) administering intratumorally to the patient an effective amount of Construct 1, wherein the effective amount of Construct 1 is about 5×107 replication-competent virus focus-forming units (RCV FFU);
and
(2) 3 weeks later administering to the patient multiple sessions, wherein each session comprises
i. administering intravenously to the patient an effective amount of Construct 2, wherein the effective amount is about 1×108 RCV FFU;
and
ii. administering intravenously to the patient an effective amount of Construct 1 at a time point around half of the session, wherein the effective amount is about 5×107 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) administering intratumorally to the patient an effective amount of Construct 1, wherein the effective amount of Construct 1 is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
(2) 3 weeks later administering to the patient multiple sessions, wherein each session comprises
i. administering intravenously to the patient an effective amount of Construct 2, wherein the effective amount is about 1×108 RCV FFU;
and
ii. administering intravenously to the patient an effective amount of Construct 1 at a time point around half of the session, wherein the effective amount is about 1×108 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising

(1) administering intratumorally to the patient an effective amount of Construct 1, wherein the effective amount of Construct 1 is about 5×108 replication-competent virus focus-forming units (RCV FFU);
and
(2) 3 weeks later administering to the patient multiple sessions, wherein each session comprises
i. administering intravenously to the patient an effective amount of Construct 2, wherein the effective amount is about 1×108 RCV FFU;
and
ii. administering intravenously to the patient an effective amount of Construct 1 at a time point around half of the session, wherein the effective amount is about 5×108 RCV FFU,
and wherein the first two sessions each lasts for 6 weeks, and the following ongoing sessions each lasts for 12 weeks.

4 more elements

A method for treating cancer in a patient in need thereof comprising administering to the patient an effective amount of Construct 1, wherein the effective amount is about 5×106, 5×107, 5×108, 1×109, or 5×109 replication-competent virus focus-forming units (RCV FFU), and wherein Construct 1 is administered intravenously with a frequency of every 3 weeks for 3 cycles and the method ends after 3 cycles.

A method for treating cancer in a patient in need thereof comprising 3 sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×107 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×107 RCV FFU,
and wherein each sessions lasts for 6 weeks, and the method ends after 3 sessions.

1 more element

A method for treating cancer in a patient in need thereof comprising 3 sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×107 RCV FFU,
and wherein each sessions lasts for 6 weeks, and the method ends after 3 sessions.

1 more element

A method for treating cancer in a patient in need thereof comprising 3 sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×108 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×108 RCV FFU,
and wherein each sessions lasts for 6 weeks, and the method ends after 3 sessions.

1 more element

A method for treating cancer in a patient in need thereof comprising 3 sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×109 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×108 RCV FFU,
and wherein each sessions lasts for 6 weeks, and the method ends after 3 sessions.

1 more element

A method for treating cancer in a patient in need thereof comprising 3 sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×109 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 1×109 RCV FFU,
and wherein each sessions lasts for 6 weeks, and the method ends after 3 sessions.

1 more element

A method for treating cancer in a patient in need thereof comprising 3 sessions, wherein each session comprises

i. administering to the patient an effective amount of Construct 2 intravenously, wherein the effective amount is about 1×109 replication-competent virus focus-forming units (RCV FFU);
and
ii. administering to the patient an effective amount of Construct 1 intravenously at a time point around half of the session, wherein the effective amount is about 5×109 RCV FFU,
and wherein each sessions lasts for 6 weeks, and the method ends after 3 sessions.

1 more element

A nucleotide sequence comprising the nucleotide sequence of SEQ ID NOs:

1 or 2.

A nucleotide sequence comprising the nucleotide sequence of SEQ ID NOs:

3, 4, 5, 6, 7, or 8.

A tri-segmented LCMV particle comprising the nucleotide sequences of SEQ ID NOs:

3, 4, and 5.

A tri-segmented PICV particle comprising the nucleotide sequences of SEQ ID NOs:

6, 7, and 8.

Dependencies are inferred from the claim text.

Cancer treatment strategies using arenavirus vectors

Life of this patent

Cancer treatment strategies using arenavirus vectors

Life of this patent

Abstract

Claims119