This Vaccine Just Changed Cancer Forever — Transcript

Full transcript

1. 0:00In the summer of 1890, a 17-year-old
2. 0:02named Bessie Dashiell, she caught her
3. 0:04hand between two train car seats, but
4. 0:06the pain just wouldn't go away. And
5. 0:08unfortunately, a biopsy found an
6. 0:09aggressive bone cancer called a sarcoma.
7. 0:12So, surgeons had to amputate her arm
8. 0:13below the elbow, but it wasn't enough.
9. 0:15The cancer had already spread, and in
10. 0:17January 1891, Bessie died. Now, her
11. 0:20surgeon was a young New Yorker named
12. 0:22William Coley, and her death broke
13. 0:24something in him. He spent weeks combing
14. 0:26through the hospital's old records for
15. 0:28anything that might have saved her. And
16. 0:30what he found in those records branded
17. 0:32him a fraud for the next 100 years. But
18. 0:34last week, 135 years later, it helped to
19. 0:37produce the first phase three win for a
20. 0:39cancer vaccine that was personalized to
21. 0:41each individual patient, and it caused
22. 0:43the stock price of Moderna, who helped
23. 0:45build this vaccine, soar by 177%
24. 0:48in a single day. That's the largest
25. 0:50single-day percentage gain in the S&P
26. 0:52500's history this century. So, deep in
27. 0:55those files, Coley found a case from
28. 0:57seven years before. So, a person by the
29. 1:00name of Fred Stein, he was a German
30. 1:01immigrant at the time. He had a sarcoma
31. 1:03of his neck that kept growing after
32. 1:05every operation. Doctors called him
33. 1:07hopeless, but then Stein caught a severe
34. 1:10strep skin infection that tore through
35. 1:12the hospital wards before antibiotics
36. 1:13existed. Now, as the infection raged
37. 1:16inside Stein's body, the tumor, it
38. 1:18melted away. Coley had to know how that
39. 1:20story ended, and he spent weeks knocking
40. 1:23on doors through the tenements of the
41. 1:24Lower East Side, and he found Stein
42. 1:27alive seven years on with no sign of
43. 1:29cancer. So, was it the immune system
44. 1:31activating to fight off the infection
45. 1:33that also caused the cancer to go away?
46. 1:36So, in 1891, Coley did something that
47. 1:38would end his career today. He took a
48. 1:40patient named Zola, who was an Italian
49. 1:43immigrant with a tumor in his tonsils
50. 1:45that was too advanced to cut out, and he
51. 1:47deliberately infected him. Zola's tumor,
52. 1:49it regressed completely, and he stayed
53. 1:51cancer-free for years before,
54. 1:53unfortunately, the tumor did come back.
55. 1:55Now, Coley turned that observation into
56. 1:57a treatment. So, what he did is he
57. 1:59killed bacteria and then he injected it,
58. 2:02known as Coley's toxins, and it was
59. 2:03given to around 1,000 patients. Now,
60. 2:06some patients did respond, but
61. 2:07unfortunately, it was remarkably few.
62. 2:10Most people didn't respond to this
63. 2:11therapy, and nobody, Coley included,
64. 2:14could predict who would respond to the
65. 2:16treatment and who wouldn't. And the
66. 2:17clinical world's patience at this time
67. 2:19ran out. In 1894, the Journal of the
68. 2:22American Medical Association delivered
69. 2:24its verdict on this approach using it
70. 2:26toxins as cures, and they labeled it a
71. 2:29complete failure. Radiation soon arrived
72. 2:32later with results that you could
73. 2:33measure and repeat, and Coley used his
74. 2:35toxins into the 1930s, but the field had
75. 2:38already moved on. Immunotherapy, as in
76. 2:41using the immune system to try and treat
77. 2:43cancer, was pushed to the margins, which
78. 2:45left a question hanging for 80 years.
79. 2:48Was Coley wrong, or was he just early?
80. 2:50Well, for most of the 20th century, it
81. 2:52looked like Coley was wrong, but in
82. 2:541976, a urologist injected the
83. 2:57tuberculosis vaccine directly into the
84. 3:00bladders of nine bladder cancer
85. 3:02patients, and it worked. 50 years later,
86. 3:04it's still the standard of care for
87. 3:06high-risk early bladder cancers. And in
88. 3:08the years that followed, the idea of
89. 3:10using the immune system to target cancer
90. 3:12grew. And at the National Institutes of
91. 3:15Health, a surgeon named Steven
92. 3:17Rosenberg, he had seen his own version
93. 3:19of the Fred Steinberg immune activation
94. 3:21miracle. In the summer of 1968, he
95. 3:24operated on a 63-year-old veteran, a
96. 3:27routine gallbladder removal, but the
97. 3:29man's chart said that he should have
98. 3:30been dead for years.
99. 3:32Surgeons had opened him up and found
100. 3:34stomach cancer that had already spread
101. 3:35to his liver. So, at the time, they
102. 3:37closed him back up. They gave him no
103. 3:39treatment, nothing whatsoever. And in
104. 3:41Rosenberg's own words, he operated to
105. 3:43remove the gallbladder, but there was no
106. 3:45remaining trace of the cancer. It's one
107. 3:47of the rarest events in medicine.
108. 3:49Something inside that patient had hunted
109. 3:51down the cancer and destroyed it and
110. 3:53Rosenberg's prime suspect was that it
111. 3:55was the immune system. So it took him
112. 3:57nearly 20 years, but by 1988 he had the
113. 4:00answer. His team pulled some immune
114. 4:02cells called T cells out of the
115. 4:04patient's own melanoma cancers and
116. 4:06multiplied them in the lab into millions
117. 4:09and then dripped them back into
118. 4:10patients' veins. In some patients the
119. 4:12tumors shrank. That was the proof that
120. 4:14he needed that by using the immune
121. 4:16system if it's properly programmed it
122. 4:18can recognize cancer and kill it. And
123. 4:20that proof is what launched a potential
124. 4:22gold rush because if T cells can already
125. 4:25recognize cancer then a vaccine should
126. 4:28be a cheap simple way to win because a
127. 4:30vaccine's whole job is to hold up a
128. 4:32target and tell the immune system to
129. 4:34attack it as in attack anything that
130. 4:36looks like this. So through the 1990s
131. 4:39there were dozens of potential cancer
132. 4:40vaccines and the field expected them to
133. 4:42work but across 1,306
134. 4:45vaccine treatments the objective
135. 4:47response rate so as in tumors that
136. 4:49actually measurably shrunk was only
137. 4:513.3%. So what was going wrong because it
138. 4:54feels like there's a potential
139. 4:55breakthrough here. Well the immune
140. 4:57system it can destroy cancer on its own
141. 4:59so Stein, Zola and Rosenberg's Veterans
142. 5:02patient proved it. T cells taken out of
143. 5:05the body and then multiplied can destroy
144. 5:07cancer. Rosenberg had proved that too
145. 5:09but the vaccines the very tool designed
146. 5:11to rally those same T cells failed in 97
147. 5:15patients out of every 100 but that
148. 5:17didn't stop companies from trying. But
149. 5:19after four huge failures in the 2000s
150. 5:21and 2010s it looked like this field was
151. 5:24done for but from those failures came
152. 5:26learnings that opened the door for a
153. 5:28success that happened last week. So
154. 5:30before you're born your immune system it
155. 5:32runs essentially a school. Every T cell
156. 5:35so the white blood cells that hunt
157. 5:36infected and cancerous cells they face
158. 5:39one more brutal final exam. Attack any
159. 5:42protein that belongs to your own body
160. 5:44and it's destroyed no exceptions. That
161. 5:46policy is why your immune system doesn't
162. 5:48just eat you alive. Now, have a look at
163. 5:50the failed cancer vaccines. Most of them
164. 5:53pointed the immune system at proteins
165. 5:55that the cancer shares with the body.
166. 5:57That's the explanation for the failures.
167. 5:59Those T cells, they were wiped out and
168. 6:01were never going to attack the cancerous
169. 6:03cells. Immunologists call the screening
170. 6:05process central tolerance. So, in 2015,
171. 6:08two immunologists put the way forward
172. 6:10into words. Cancer's own mutations
173. 6:12create brand new proteins that exist
174. 6:14nowhere else in the body. So, these
175. 6:16newer antigens, so neo as in new, the
176. 6:19body's school has never seen them. So,
177. 6:21the T cells that can attack these
178. 6:22cancerous proteins, they've never been
179. 6:24deleted. They're still in the army
180. 6:26waiting for a target to attack, which
181. 6:28leaves one problem. Your tumor's
182. 6:30mutations, they're not the same as my
183. 6:32tumor's mutations. So, every single
184. 6:34patient is different. A shelf vaccine,
185. 6:36it's never going to work. What we need
186. 6:38is a personalized approach, a
187. 6:40personalized vaccine per patient. So,
188. 6:42here's what's required. First, we need
189. 6:44to sequence the patient's tumor and then
190. 6:46their healthy blood and then we need to
191. 6:47subtract so that we're only left with
192. 6:50what's mutated in the tumor and not the
193. 6:52healthy cells. Second, we need to be
194. 6:54able to predict which of those mutant
195. 6:56fragments the patient's own immune
196. 6:57system can actually display on the
197. 6:59surface of the cell so that the immune
198. 7:01system can then latch onto them and
199. 7:02attack them. An immune system, if they
200. 7:04can't see that, it's useless. So, neural
201. 7:07AI networks is what does that prediction
202. 7:09for us. And Moderna's own selection
203. 7:11algorithm, it is proprietary and it is
204. 7:13unpublished, but we do know what it
205. 7:15does. It predicts what's displayable and
206. 7:18it picks up to 34 targets. Third is that
207. 7:20we need to encode up to 34 of these
208. 7:22targets on a single strand of mRNA, wrap
209. 7:25it up into a microscopic fat droplet, so
210. 7:28a lipid nanoparticle, and then inject it
211. 7:30into the patient. And in July 2017, that
212. 7:33process was tested in 13 humans with
213. 7:35melanoma, five of which already had
214. 7:37metastatic disease. And after these
215. 7:40patients had their personalized vaccine,
216. 7:42eight who were disease-free at the
217. 7:43vaccination date, they stayed
218. 7:45recurrence-free for up to 23 months. And
219. 7:47then a team in Boston vaccinated six
220. 7:50melanoma patients with protein fragments
221. 7:52rather than RNA. Four of the six stayed
222. 7:55recurrence-free at the 25-month mark,
223. 7:57and two of those whose cancer had
224. 7:59progressed, they completely regressed
225. 8:02once an anti-PD-1 checkpoint drug was
226. 8:04added. But building a bespoke drug for
227. 8:06one patient at a time using technology
228. 8:08at the time was incredibly expensive.
229. 8:11But then the world was handed the exact
230. 8:12technology used to scale up this
231. 8:14concept. So you will already know this
232. 8:16part, the mRNA technology for COVID.
233. 8:19Researchers used the mRNA vaccine
234. 8:21technology to develop personalized
235. 8:23therapies for 157 patients with resected
236. 8:27melanoma, as in people who had the
237. 8:29tumors cut out and were waiting to learn
238. 8:31whether those tumors would come back.
239. 8:33This was a randomized control trial, and
240. 8:34again, we had personalized mRNA vaccines
241. 8:37plus the checkpoint drug Keytruda or
242. 8:40Keytruda alone. In December 2022, here
243. 8:43was the result. The recurrence risk was
244. 8:45down by roughly 44%. So Merck and
245. 8:48Moderna, they ran a large follow-up
246. 8:50phase 3 trial, a double-blind
247. 8:52placebo-controlled study. And on August
248. 8:5419th, 2026, here are the results. The
249. 8:57trial involved 1,137
250. 9:00patients with completely resected stage
251. 9:022B to stage 4 melanoma. So this was
252. 9:06cancer removed by surgery and were at
253. 9:08high risk of it coming back. They were
254. 9:10randomized into two groups. So one had
255. 9:12the personalized therapy plus Keytruda
256. 9:14versus Keytruda alone. So whatever
257. 9:17benefit appeared was on top of the
258. 9:19standard treatment, not instead of it.
259. 9:21And here's the wonderful news. The
260. 9:22combination treatment, it successfully
261. 9:24met its endpoint, meaning that it
262. 9:26delivered greater results than Keytruda
263. 9:28alone. Now we don't have the numbers
264. 9:30yet, but in the preceding phase 2 study,
265. 9:32there was a 49% reduction in the risk of
266. 9:35recurrence or death compared to Keytruda
267. 9:37alone, and a 59% reduction in the risk
268. 9:40of distant metastases or death compared
269. 9:42to Keytruda alone. There were also no
270. 9:44new safety signals observed. The
271. 9:46companies describe it as the first
272. 9:48positive phase three trial ever for an
273. 9:50individualized neoantigen therapy, and
274. 9:52the first for any mRNA-based cancer
275. 9:54treatment. But, as Patreon member Red
276. 9:56asks, for what kinds of cancers do these
277. 9:59vaccines work? Do they cure cancer, or
278. 10:01is it just an increase in treatment and
279. 10:03survival rates by a little bit? Well,
280. 10:05this is for melanoma treatment. It's not
281. 10:07prevention, and it's not a cure, but a
282. 10:09preventive vaccine is already here for
283. 10:11cancer, and that is the HPV vaccine. It
284. 10:13blocks the virus behind most cervical
285. 10:16cancers, and in the US, cancer deaths
286. 10:18from cervical cancer have fallen by more
287. 10:20than 60% in over a decade. But, as
288. 10:23Patreon member Blessy points out, yes,
289. 10:25this treatment, it did work on melanoma,
290. 10:27so is it reasonable to be hopeful that
291. 10:29this should also work for other types of
292. 10:30tumors as well? Based on my
293. 10:32understanding of the mechanism, it seems
294. 10:34like it should. Moderna chose melanoma
295. 10:36to start with because melanoma is one of
296. 10:38the most heavily mutated cancers there
297. 10:40are, so it's got the most raw material
298. 10:42for neoantigens. So, in theory, it's one
299. 10:44of the easier cancers to build these
300. 10:46personalized treatments for. But, the
301. 10:47good news is that Merck and Moderna
302. 10:49alone, they are running nine trials of
303. 10:51this therapy. So, two in melanoma, four
304. 10:54in lung cancer, three already at phase
305. 10:56three, one in kidney, and two in
306. 10:58bladder. And buried in that list is one
307. 11:00of my favorite details in this entire
308. 11:01story. So, in high-risk early bladder
309. 11:04cancer patients, it's being trialed
310. 11:05alongside BCG. So, that's the same
311. 11:08tuberculosis vaccine that was started in
312. 11:101976.
313. 11:12So, in my view, the main reason why
314. 11:14Moderna stock price has jumped up so
315. 11:16much is because there's so much hope
316. 11:18that this personalized treatment can
317. 11:19then be translated onto other types of
318. 11:21cancer. And this whole field is much
319. 11:23bigger than just one partnership. So, in
320. 11:25May, there was a study published in
321. 11:27Nature Reviews Drug Discovery, and they
322. 11:29mapped out the whole clinical pipeline
323. 11:31of therapeutic cancer vaccines. And
324. 11:33Patreon member David Sprouse asks the
325. 11:35money question. Any idea how affordable
326. 11:38it is expected to be given the need for
327. 11:40customization and the extra work
328. 11:41involved? Well, the truthful answer is
329. 11:43that at this stage we don't know what
330. 11:44the costs will be. This therapy isn't
331. 11:46yet FDA approved and it's not available
332. 11:48to the general public, but we do have
333. 11:50reason to be hopeful. With this
334. 11:52breakthrough will come further
335. 11:53innovation and it's a really exciting
336. 11:55path forward, particularly if we see
337. 11:56positive results from the other cancer
338. 11:59vaccines that are in the pipeline. And
339. 12:00it's not just cancer vaccines where
340. 12:02we're getting these amazing results.
341. 12:04Recently there was a fantastic result
342. 12:05published about pancreatic cancer and
343. 12:07I'll go through the results in this
344. 12:09video here. And I've put the full
345. 12:10write-up of this video, so the
346. 12:12transcript and every study that I've
347. 12:13cited over at drstanfield.com. Link is
348. 12:16in the pinned comment. And if you want
349. 12:17early access to videos like this, as
350. 12:19well as access to the Discord server,
351. 12:21make sure to check out Patreon or join
352. 12:23as a channel member.